PD-L1 Cancer Research Results

PD-L1, Programmed Death-Ligand 1: Click to Expand ⟱

Source:

Type:

PD-L1 is a protein that plays a crucial role in the regulation of the immune system. PD-L1 helps to prevent the immune system from attacking healthy cells by binding to its receptor, PD-1, on immune cells. However, some cancer cells can exploit this mechanism by expressing high levels of PD-L1, which can help them evade immune detection.
PD-L1 has become a key target for cancer immunotherapy, particularly in the development of checkpoint inhibitors.

PD-1: Upregulated on tumor-infiltrating lymphocytes (TILs), reflecting chronic antigen exposure and an “exhausted” T cell phenotype.
PD-L1 and PD-L2: Frequently overexpressed by many tumor types (e.g., non–small cell lung cancer, melanoma, renal cell carcinoma, head and neck cancers.

Scientific Papers found: Click to Expand⟱

1027-

AG,

Astragalus polysaccharide (APS) attenuated PD-L1-mediated immunosuppression via the miR-133a-3p/MSN axis in HCC

vitro+vivo,

HCC,

SMMC-7721 cell

ntraperitoneally injected with 100, 200 and 400 mg/kg APS for 12 days

4.2 mg/mL

mice

PD-L1↓,
miR-133a-3p↝,

5434-

AG,

Recent Advances in the Mechanisms and Applications of Astragalus Polysaccharides in Liver Cancer Treatment: An Overview

Review,

Liver,

AntiCan↑, Preclinical studies indicate that APS exerts significant anti-liver cancer effects through multiple biological actions, including the promotion of apoptosis, inhibition of proliferation, suppression of epithelial–mesenchymal transition, regulation of
Apoptosis↑,
TumCP↓,
EMT↓,
Imm↑, improving host immune response
ChemoSen↑, APS exhibits synergistic effects when combined with conventional chemotherapeutics and interventional treatments such as transarterial chemoembolisation, improving efficacy and reducing toxicity.
BioAv↓, limitations such as low bioavailability and a lack of large-scale clinical trials remain challenges for clinical translation.
TumCG↓, APS significantly inhibited tumour growth in H22-bearing mice with a dose-dependent effect (100, 200, 400 mg/kg), with the 400 mg/kg group achieving a tumour inhibition rate of 59.01%
IL2↑, APS enhance the thymus and spleen indices and elevates the key cytokines, including IL-2, IL-12, and TNF-α.
IL12↑,
TNF-α↑,
P-gp/ABCB1↓, APS reversed chemoresistance by downregulating P-glycoprotein and MDR1 mRNA expression
MDR1↓,
QoL↑, These effects contributed to improved treatment tolerance and enhanced quality of life [39].
Casp↑, APS can activate both the intrinsic and extrinsic apoptotic pathways, leading to caspase activation and DNA fragmentation
DNAdam↑,
Bcl-2↓, Mechanistically, APS downregulate antiapoptotic proteins such as Bcl-2 while upregulating proapoptotic proteins such as Bax and cleaved caspase-3.
BAX↑,
MMP↓, APS have been shown to disrupt the mitochondrial membrane potential and promote the release of cytochrome c, thereby enhancing apoptotic cascades in hepatocellular carcinoma models.
Cyt‑c↑,
NOTCH1↓, APS (0.1, 0.5, and 1.0 mg/mL) were shown to reduce both mRNA and protein levels of Notch1 in a concentration-dependent manner.
GSK‐3β↓, APS significantly inhibited the proliferation of HepG2 cells by downregulating the expression of glycogen synthase kinase-3β (GSK-3β), with 200 μg/mL being the most effective concentration.
TumCCA↑, APS exerted these effects by inducing cell cycle arrest at the G2/M and S phases, thereby impeding tumour cell proliferation [35].
GSH↓, HepG2 cells. APS also reduced intracellular glutathione (GSH) levels, increased reactive oxygen species (ROS) and lipid peroxidation levels, and elevated intracellular iron ion concentrations—all in a dose-dependent manner.
ROS↑,
lipid-P↑,
c-Iron↑,
GPx4↓, APS treatment led to the downregulation of GPX4 and upregulation of ACSL4, indicating that APS promotes ferroptosis in liver cancer cells.
ACSL4↑,
Ferroptosis↑,
Wnt↓, inhibit the expression of key proteins involved in the Wnt/β-catenin signalling pathway
β-catenin/ZEB1↓,
cycD1/CCND1↓, by downregulating the key oncogenic targets, including β-catenin, C-myc, and cyclin D1, which subsequently reduces Bcl-2 expression and activates the apoptotic cascade in HepG2 liver cancer cells.
Akt↓, It also inhibited the Akt/p-Akt signalling pathway.
PI3K↓, APS inhibit the PI3K/AKT/mTOR signalling pathway, which is a central negative regulator of autophagy.
mTOR↓,
CXCR4↓, PS upregulated the epithelial marker E-cadherin while downregulating the mesenchymal marker vimentin and the chemokine receptor CXCR4 at both mRNA and protein levels, suggesting that APS suppress liver cancer cell growth and metastasis by inhibiting
Vim↓,
PD-L1↓, APS interfere with immune checkpoint signalling by downregulating Programmed death-ligand 1 (PD-L1) expression on tumour cells.
eff↑, The preparation of polysaccharide–SeNP composites typically involves using sodium selenite (Na2SeO3) as the precursor and ascorbic acid (Vc) as the reducing agent, with synthesis carried out via a chemical reduction method in a polysaccharide solutio
eff↑, Mechanistic investigations revealed that AASP–SeNPs elevated intracellular ROS levels and reduced the mitochondrial membrane potential (∆Ψm).
ChemoSen↑, APS enhance doxorubicin-induced endoplasmic reticulum (ER) stress by reducing O-GlcNAcylation levels, thereby promoting apoptosis of liver cancer cells.
ChemoSen↑, APS inhibited BEL-7404 human liver cancer cell growth in a concentration-dependent manner and showed stronger cytotoxicity when combined with cisplatin.
chemoP↑, APS protects against chemotherapy-induced liver injury, particularly that caused by CTX, through antiapoptotic mechanisms

5437-

AG,

Modulation of PD-L1 by Astragalus polysaccharide attenuates the induction of melanoma stem cell properties and overcomes immune evasion

in-vivo,

Melanoma,

B16-F10

mice

CSCs↓, APS attenuated the tumor sphere formation of MSCs in vitro as well as the tumorigenicity in vivo.
CD133↓, It also decreased the expression of CD133, BMI1 and CD47.
BMI1↓,
PD-L1↓, it was confirmed that APS inhibited the induction of MSCs by down-regulating PD-L1 expression.
TumCG↓, Accordingly, the CSC properties were also attenuated, accompanied by a slower tumor growth rate. F

337-

AgNPs,

immuno,

Silver nanoparticle induced immunogenic cell death can improve immunotherapy

Review,

NA,

PD-L1↓, deliver therapeutic agents

1023-

AL,

Allicin May Promote Reversal of T-Cell Dysfunction in Periodontitis via the PD-1 Pathway

in-vitro,

NA,

5, 10, 25, and 50 μM

100 and 250 μM were toxic to T cells

Analysis,

NA,

PD-L1↓, We concluded from the in-silico data that allicin could possibly be an inhibitor of PD-L1.

1024-

Api,

CUR,

Apigenin suppresses PD-L1 expression in melanoma and host dendritic cells to elicit synergistic therapeutic effects

vitro+vivo,

Melanoma,

A375

 (30 μM) for 24 h

in-vitro,

Melanoma,

A2058

in-vitro,

Melanoma,

RPMI-7951

TumCG↓,
Apoptosis↑,
PD-L1↓, IFN-γ-induced PD-L1 upregulation was significantly inhibited by flavonoids, especially apigenin
STAT1↓,
tumCV↓,
T-Cell↑, Curcumin and apigenin enhance T cell-mediated melanoma cell killing

1026-

ART/DHA,

PD-L1_therapy_in_T-cell_lymphoma">Artemisinin improves the efficiency of anti-PD-L1 therapy in T-cell lymphoma

Ferroptosis↑,
ROS↑,
ERK↓,
PD-L1↓, combination therapy with artemisinin greatly improved the anti-lymphoma effciency of anti-PD-L1 monoclonal antibody.

5415-

ASA,

The Anti-Metastatic Role of Aspirin in Cancer: A Systematic Review

Review,

Var,

TumMeta↓, The included studies demonstrated that aspirin suppresses metastatic dissemination across multiple cancer types through coordinated platelet-dependent and tumor-intrinsic mechanisms.
COX1↓, Aspirin consistently inhibited platelet aggregation and COX-1-dependent TXA2 production, disrupting platelet–tumor cell interactions, intravascular metastatic niche formation, and platelet-mediated immune suppression.
TXA2↓,
AntiAg↑, Beyond platelet effects, aspirin suppressed EMT, migration, and invasion through modulation of EMT transcriptional regulators and inflammatory signaling pathways.
EMT↓,
TumCMig↓,
TumCI↓,
AMPK↑, Additional mechanisms included activation of AMPK, inhibition of c-MYC signaling, regulation of redox-responsive pathways and impairment of anoikis resistance.
cMyc↓,
PGE2↓, Importantly, oral aspirin (20 mg/kg/day; human-equivalent ≈ 150 mg/day), administered before tumor cell injection, prevented platelet-induced metastatic enhancement and suppressed TXA2 and PGE2 production.
Dose↑, medium and high doses of aspirin reduced pulmonary metastatic burden by more than 50%, whereas low-dose aspirin was ineffective.
RadioS↑, Wang et al. [45] demonstrated that low-dose aspirin suppresses radiotherapy-induced release of immunosuppressive exosomes in breast cancer, restoring NK-cell proliferation and enhancing antitumor immunity in vivo.
PD-L1↓, Similarly, Xiao et al. [46] showed that aspirin epigenetically downregulates PD-L1 expression by inhibiting KAT5-dependent histone acetylation, thereby restoring T-cell activation
E-cadherin↑, Aspirin restored E-cadherin expression and suppressed EMT regulators, including Slug, vimentin, Twist, MMP-2, and MMP-9.
EMT↓,
Slug↓,
Vim↓,
Twist↓,
MMP2↓,
MMP9↓,
other↑, definitive conclusions regarding clinical efficacy across cancer types cannot yet be drawn. Nevertheless, the consistency of mechanistic signals across experimental systems supports further investigation of aspirin as a low-cost adjunct in oncology

1028-

ASA,

Aspirin Suppressed PD-L1 Expression through Suppressing KAT5 and Subsequently Inhibited PD-1 and PD-L1 Signaling to Attenuate OC Development

vitro+vivo,

Ovarian,

TumCP↓,
TumW↓,
PD-L1↓,
Ki-67↓,
H3K27ac∅, ASP downregulated KAT5 expression and blocked this phenomenon.
eff↑, effect of antiPD-L1 therapy

5568-

B-Gluc,

immuno,

Beta-glucans in oncology: revolutionizing treatment with immune power & tumor targeting

Review,

Var,

TNF-α↓, Beta-glucans suppress pro-inflammatory cytokines (e.g., TNF-α, IL-6) and tumor-promoting pathways like NF-κB, while modulating T-regulatory cells (Tregs) and downregulating PD-L1 to overcome immune evasion.
IL6↓,
NF-kB↓,
PD-L1↓,
Imm↑,
BAX↑, They induce apoptosis via Bax/Bcl-2 regulation, arrest cell cycles at G1/S or G2/M phases, and inhibit angiogenesis by targeting VEGF and MMPs.
Bcl-2↓,
TumCCA↑,
angioG↓,
VEGF↓,
MMPs↓,
OS↑, improved overall survival (OS) in melanoma (hazard ratio
chemoP↑, alongside reduced chemotherapy toxicity
eff↑, Synergy with PD-1/PD-L1 inhibitors enhances immunotherapy efficacy, particularly in immunogenic tumors.
BioAv↑, Advanced nano-delivery systems, including micelles and exosomes, improve bioavailability and tumor targeting.

5580-

B-Gluc,

Lentinan, a Shiitake Mushroom β-Glucan, Downregulates the Enhanced PD-L1 Expression Induced by Platinum Compounds in Gastric Cancer Cells

in-vitro,

GC,

MKN45

PD-L1↓, lentinan treatment inhibited the platinum drug-stimulated expression of PD-L1 in gastric cancer cells mainly by suppressing MAPK signaling
MAPK↓,
OS↑, Lentinan has been reported to improve the overall survival of cancer patients receiving chemotherapy [23, 24] through its antitumor and immunomodulatory activitie
AntiTum↑,
Imm↑,

1029-

Ba,

BA,

Baicalein and baicalin promote antitumor immunity by suppressing PD-L1 expression in hepatocellular carcinoma cells

vitro+vivo,

HCC,

PD-L1↓, PD-L1 upregulation induced by interferon-γ (IFN-γ) was significantly inhibited by these two flavonoids in vitro
T-Cell↑, Both baicalein and baicalin enhanced the cytotoxicity of T cells to eliminate tumor cells
STAT3↓,

5507-

Ba,

Baicalein Enhances Radiosensitivity in Colorectal Cancer via JAK2/STAT3 Pathway Inhibition

vitro+vivo,

Var,

RadioS↑, Our results demonstrated that BE significantly increased radiosensitivity in vitro and in vivo and enhanced apoptosis in tumor tissues
p‑STAT3↓, BE significantly downregulated the expression of p-STAT3, JAK2, and PD-L1, and significantly upregulated SOCS3 expression.
JAK2↓,
PD-L1↓,
SOCS-3↑,

2292-

Ba,

BA,

Baicalin and baicalein in modulating tumor microenvironment for cancer treatment: A comprehensive review with future perspectives

Review,

Var,

AntiCan↑, Baicalin and baicalein exhibit anticancer activities against multiple cancers with extremely low toxicity to normal cells.
*toxicity↓,
BioAv↝, Baicalein permeates easily through the epithelium from the gut lumen to the blood underneath due to its low molecular mass and high lipophilicity, albeit a low presence of its transporters.
BioAv↓, In contrast, baicalin has limited permeability partly due to its larger molecular mass and higher hydrophilicity [24]. The overall low water solubility of baicalin and baicalein contributes to their poor bioavailability.
*ROS↓, baicalin protected macrophages against mycoplasma gallisepticum (MG)-induced ROS production and NLRP3 inflammasome activation by upregulating autophagy and TLR2-NFκB pathway
*TLR2↓,
*NF-kB↓,
*NRF2↑, Therefore, baicalin exerts strong antioxidant activity by activating NRF2 antioxidant program.
*antiOx↑,
*Inflam↓, These data suggest that by attenuating ROS and inflammation baicalein inhibits tumor formation and metastasis.
HDAC1↓, baicalein reduced CTCLs by inhibiting HDAC1 and HDAC8 and its effect on tumor inhibition was better than traditional HDAC inhibitors
HDAC8↓,
Wnt↓, Baicalein also reduced the proliferation of acute T-lymphoblastic leukemia (TLL) Jurkat cells by inhibiting the Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
PD-L1↓, baicalein and baicalin promoted antitumor immune response by suppressing PD-L1 expression of HCC cells, thus increasing tumor regression
Sepsis↓, Baicalein can also attenuate severe sepsis via ameliorating immune dysfunction of T lymphocytes.
NF-kB↓, downregulation of NFκB and CD74/CD44 signaling in EBV-transformed B cells
LOX1↓, baicalein is considered to be an inhibitor of lipoxygenases (LOXs)
COX2/PTGS2↓, inhibits the expression of NF-κB/p65 and COX-2
VEGF↑, Baicalin was shown to suppress the expression of VEGF, resulting in the inhibition of PI3K/AKT/mTOR pathway and reduction of proliferation and migration of human mesothelioma cells
PI3K↓,
Akt↓,
mTOR↓,
MMP2↓, baicalin suppressed expression of MMP-2 and MMP-9 via restriction of p38MAPK signaling, resulting in reduced breast cancer cell growth, invasion
MMP9↓,
SIRT1↑, The inhibition of MMP-2 and MMP-9 expression in NSCLC cells is mediated by activating the SIRT1/AMPK signaling pathway.
AMPK↑,

2296-

Ba,

The most recent progress of baicalein in its anti-neoplastic effects and mechanisms

Review,

Var,

CDK1↓, graphical abstract
Cyc↓,
p27/CDKN1B↑,
P21↑,
P53↑,
TumCCA↑, Cell cycle arrest
TumCI↓, Inhibit invastion
MMP2↓,
MMP9↓,
E-cadherin↑,
N-cadherin↓,
Vim↓,
LC3A↑,
p62↓,
p‑mTOR↓,
PD-L1↓,
CAFs/TAFs↓,
VEGF↓,
ROCK1↓,
Bcl-2↓,
Bcl-xL↓,
BAX↑,
ROS↑,
cl‑PARP↑,
Casp3↑,
Casp9↑,
PTEN↑, A549, H460
MMP↓, ↓mitochondrial transmembrane potential, redistribution of cytochrome c,
Cyt‑c↑,
Ca+2↑, ↑Ca2+
PERK↑, ↑PERK, ↑IRE1α, ↑CHOP,
IRE1↑,
CHOP/DDIT3↑,
Copper↑, ↑Cu+2
Snail↓, ↓Snail, ↓vimentin, ↓Twist1,
Vim↓,
Twist↓,
GSH↓, ↑ROS, ↓GSH, ↑MDA, ↓MMP, ↓NRF2, ↓HO-1, ↓GPX4, ↓FTH1, ↑TFR1, ↓p-JAK2, ↓p-STAT3
NRF2↓,
HO-1↓,
GPx4↓,
XIAP↓, ↓Bcl-2, ↓Bcl-xL, ↓XIAP, ↓surviving
survivin↓,
DR5↑, ↑ROS, ↑DR5

2290-

Ba,

Research Progress of Scutellaria baicalensis in the Treatment of Gastrointestinal Cancer

Review,

GI,

p‑mTOR↓, Baicalein treatment decreased the expression levels of p-mTOR, p-Akt, p-IκB and NF-κB proteins, and suppressed GC cells by inhibiting the PI3K/Akt
p‑Akt↓,
p‑IKKα↓,
NF-kB↓,
PI3K↓,
Akt↓,
ROCK1↓, Baicalin reduces HCC proliferation and metastasis by inhibiting the ROCK1/GSK-3β/β-catenin signaling pathway
GSK‐3β↓,
CycB/CCNB1↓, Baicalein induces S-phase arrest in gallbladder cancer cells by down-regulating Cyclin B1 and Cyclin D1 in gallbladder cancer BGC-SD and SGC996 cells while up-regulating Cyclin A
cycD1/CCND1↓,
cycA1/CCNA1↑,
CDK4↓, Following baicalein treatment, there is a down-regulation of Ezrin, CyclinD1, and CDK4, as well as an up-regulation of p53 and p21 protein levels, thereby leading to the induction of CRC HCT116 cell cycle arrest
P53↑,
P21↑,
TumCCA↑,
MMP2↓, baicalein was able to inhibit the metastasis of gallbladder cancer cells by down-regulating ZFX, MMP-2 and MMP-9.
MMP9↓,
EMT↓, Baicalein treatment effectively inhibits the snail-induced EMT process in CRC HT29 and DLD1 cells
Hif1a↓, Baicalein inhibits VEGF by downregulating HIF-1α, a crucial regulator of angiogenesis
Shh↓, baicalein inhibits the metastasis of PC by impeding the Shh pathway
PD-L1↓, Baicalin and baicalein down-regulate PD-L1 expression induced by IFN-γ by reducing STAT3 activity
STAT3↓,
IL1β↓, baicalein therapy significantly diminishes the levels of pro-inflammatory cytokines such as interleukin-1 beta (IL-1β), IL-2, IL-6, and GM-CSF
IL2↓,
IL6↓,
PKM2↓, Baicalein, by reducing the expression levels of HIF-1A and PKM2, can inhibit the glycolysis process in ESCC cells
HDAC10↓, Baicalein treatment increases the level of miR-3178 and decreases HDAC10 expression, resulting in the inactivation of the AKT signaling pathways.
P-gp/ABCB1↓, baicalein reverses P-glycoprotein (P-gp)-mediated resistance in multidrug-resistant HCC (Bel7402/5-FU) cells by reducing the levels of P-gp and Bcl-xl
Bcl-xL↓,
eff↓, Baicalein combined with gemcitabine/docetaxel promotes apoptosis of PC cells by activating the caspase-3/PARP signaling pathway
BioAv↓, baicalein suffers from low water solubility and susceptibility to degradation by the digestive system
BioAv↑, Encapsulation of baicalein into liposomal bilayers exhibits a therapeutic efficacy close to 90% for PDAC

1030-

BBR,

Berberine diminishes cancer cell PD-L1 expression and facilitates antitumor immunity via inhibiting the deubiquitination activity of CSN5

in-vitro,

Lung,

H460

0–20 μmol/L 24hr

lewis tumor xenograft mice

PD-L1↓,
TumCG↓,
Ki-67↓,
cl‑Casp3↑,

1031-

BCA,

Biochanin A Suppresses Tumor Progression and PD-L1 Expression via Inhibiting ZEB1 Expression in Colorectal Cancer

vitro+vivo,

CRC,

HCT116

20-100uM

vitro+vivo,

CRC,

SW-620

PD-L1↓,
TumCG↓,
Zeb1↓, ZEB1 is a main regulator of PD-L1 expression in CRC.
E-cadherin↑,
N-cadherin↓,
EMT↓, blocked the EMT process in CRC.

1032-

Buty,

Gut microbiome-derived butyrate inhibits the immunosuppressive factors PD-L1 and IL-10 in tumor-associated macrophages in gastric cancer

in-vivo,

GC,

AGS

human and mice

GutMicro↑, Restoration of the intestinal microbiome and its metabolic functions inhibit tumor growth The abundances of Faecalibacterium and Bifidobacterium in the intestinal flora were lower in GC patients than in healthy individuals.
PD-L1↓, Butyrate, a representative microbiome metabolite, suppressed the expression levels of PD-L1 and IL-10 in immune cells.
IL10↓,
TumCG↓, Butyrate inhibited tumor growth in mice

2017-

CAP,

Spice Up Your Kidney: A Review on the Effects of Capsaicin in Renal Physiology and Disease

Review,

Var,

RenoP↑, observed experimental benefits in preventing acute kidney injury
AntiTum↑, anti-tumoral properties of capsaicin on different types of cancer cells are well-acknowledged
AMPK↑, activating the AMPK/mTOR
mTOR↑,
PD-1↓, capsaicin promotes the inhibition of the PD-L1/PD-1 checkpoint
PD-L1↓,

6017-

CGA,

Therapeutic Potential of Chlorogenic Acid in Chemoresistance and Chemoprotection in Cancer Treatment

Review,

Var,

AntiCan↑, Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms.
*chemoP↑, CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals effectively.
TNF-α↓, CGA reduces inflammation levels in renal tissues by down-regulating tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2),
COX2/PTGS2↓,
IL6↓, Moreover, CGA exhibits a protective effect against 5-FU-induced ovarian tissue damage, reducing Interleukin 6 (IL-6) levels;
eff↑, CGA suppresses the expression of Programmed Cell Death Ligand 1 (PD-L1) on cancer cells, boosting the antitumor effect of the anti-PD-1 antibody and enhancing anticancer immunotherapy
PD-L1↓,
*cognitive↓, CGA, have shown promise in preventing cognitive dysfunction and suppressing amyloid β plaques
*Aβ↓,
*TAC↑, hyperlipidemic patients who ingested 200 mL of Mate tea (12.5 mg/mL) daily experienced a significant increase in serum total antioxidant status and the enzymatic activity of superoxide dismutase (SOD),
*SOD↑,
*eff↑, In blueberry jam production, the high-temperature processing of blueberries with sucrose promoted the formation of 11 CGA derivatives
*eff↑, roasting process (170 to 200 °C/10 to 30 min) of coffee beans promotes CGA transformation to four chlorogenic acid lactones
ChemoSen↑, CGA was found to increase the sensitivity of hepatocellular carcinoma cells to 5-FU treatment
tumCV↓, CGA was shown to collaborate by significantly reducing cell viability and growth through induction of apoptosis, attributed to inhibition of extracellular signal-regulated kinases (ERKs)
Apoptosis↑,
ERK↓,
chemoP↑, Protective Role of Chlorogenic Acid against Toxicity Induced by Chemotherapy
*GPx↑, figure4
*GSTs↑,
*GSH↑,
*SOD↑,
*Catalase↑,
*ROS↓,
*lipid-P↓,
*MDA↓,
*Casp3↓,
*HO-1↓,
cardioP↑, reported the cardioprotective effect of CGA against doxorubicin-induced cardiotoxicity in female Swiss albino mice.
radioP↑, The radioprotective potential of CGA against γ-radiation-induced chromosomal damage in male albino Swiss mice was initially demonstrated in 1993.

1244-

CGA,

immuno,

Cancer Differentiation Inducer Chlorogenic Acid Suppresses PD-L1 Expression and Boosts Antitumor Immunity of PD-1 Antibody

in-vivo,

NA,

murine tumor xenografts

PD-L1↓,
T-Cell↑,
eff↑, boosting the antitumor effect of the anti-PD-1 antibody.

6136-

CHr,

Tras,

Synergistic anticancer effects of Chrysin and trastuzumab in HER2-Positive breast cancer cells

in-vitro,

BC,

SkBr3

in-vitro,

BC,

BT474

in-vitro,

Nor,

MCF10

eff↑, Chrysin enhanced the anticancer effects of trastuzumab, achieving an optimal combination index (CI) of 0.39 in SKBR3 cells and a similarly strong synergistic profile in BT-474 cells (CI = 0.54).
HER2/EBBR2↓, chrysin also reduced HER2 expression in a significant manner
p‑STAT3↓, combination therapy significantly decreased p-STAT3 and PD-L1 protein levels in SKBR3 and reduced mRNA levels of Tie2 and VEGFR2 in both cell lines.
PD-L1↓,
ChemoSen↑, Chrysin synergistically enhances the efficacy of trastuzumab in HER2-positive SKBR3 and BT-474 breast cancer cells.

2781-

CHr,

PBG,

Chrysin a promising anticancer agent: recent perspectives

Review,

Var,

PI3K↓, It can block Phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling in different animals against various cancers
Akt↓,
mTOR↓,
MMP9↑, Chrysin strongly suppresses Matrix metalloproteinase-9 (MMP-9), Urokinase plasminogen activator (uPA) and Vascular endothelial growth factor (VEGF), i.e. factors that can cause cancer
uPA↓,
VEGF↓,
AR↓, Chrysin has the ability to suppress the androgen receptor (AR), a protein necessary for prostate cancer development and metastasis
Casp↑, starts the caspase cascade and blocks protein synthesis to kill lung cancer cells
TumMeta↓, Chrysin significantly decreased lung cancer metastasis i
TumCCA↑, Chrysin induces apoptosis and stops colon cancer cells in the G2/M cell cycle phase
angioG↓, Chrysin prevents tumor growth and cancer spread by blocking blood vessel expansion
BioAv↓, Chrysin’s solubility, accessibility and bioavailability may limit its medical use.
*hepatoP↑, As chrysin reduced oxidative stress and lipid peroxidation in rat liver cells exposed to a toxic chemical agent.
*neuroP↑, Protecting the brain against oxidative stress (GPx) may be aided by increasing levels of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx).
*SOD↑,
*GPx↑,
*ROS↓, A decrease in oxidative stress and an increase in antioxidant capacity may result from chrysin’s anti-inflammatory properties
*Inflam↓,
*Catalase↑, Supplementation with chrysin increased the activity of antioxidant enzymes like SOD and catalase and reduced the levels of oxidative stress markers like malondialdehyde (MDA) in the colon tissue of the rats.
*MDA↓, Antioxidant enzyme activity (SOD, CAT) and oxidative stress marker (MDA) levels were both enhanced by chrysin supplementation in mouse liver tissue
ROS↓, reduction of reactive oxygen species (ROS) and oxidative stress markers in the cancer cells further indicated the antioxidant activity of chrysin
BBB↑, After crossing the blood-brain barrier, it has been shown to accumulate there
Half-Life↓, The half-life of chrysin in rats is predicted to be close to 2 hours.
BioAv↑, Taking chrysin with food may increase the effectiveness of the supplement: increased by a factor of 1.8 when taken with a high-fat meal
ROS↑, In contrast to 5-FU/oxaliplatin, chrysin increases the production of reactive oxygen species (ROS), which in turn causes autophagy by stopping Akt and mTOR from doing their jobs
eff↑, mixture of chrysin and cisplatin caused the SCC-25 and CAL-27 cell lines to make more oxygen free radicals. After treatment with chrysin, cisplatin, or both, the amount of reactive oxygen species (ROS) was found to have gone up.
ROS↑, When reactive oxygen species (ROS) and calcium levels in the cytoplasm rise because of chrysin, OC cells die.
ROS↑, chrysin is the cause of death in both types of prostate cancer cells. It does this by depolarizing mitochondrial membrane potential (MMP), making reactive oxygen species (ROS), and starting lipid peroxidation.
lipid-P↑,
ER Stress↑, when chrysin is present in DU145 and PC-3 cells, the expression of a group of proteins that control ER stress goes up
NOTCH1↑, Chrysin increased the production of Notch 1 and hairy/enhancer of split 1 at the protein and mRNA levels, which stopped cells from dividing
NRF2↓, Not only did chrysin stop Nrf2 and the genes it controls from working, but it also caused MCF-7 breast cancer cells to die via apoptosis.
p‑FAK↓, After 48 hours of treatment with chrysin at amounts between 5 and 15 millimoles, p-FAK and RhoA were greatly lowered
Rho↓,
PCNA↓, Lung histology and immunoblotting studies of PCNA, COX-2, and NF-B showed that adding chrysin stopped the production of these proteins and maintained the balance of cells
COX2/PTGS2↓,
NF-kB↓,
PDK1 / PDPK1↓, After the chrysin was injected, the genes PDK1, PDK3, and GLUT1 that are involved in glycolysis had less expression
PDK3↑,
GLUT1↓,
Glycolysis↓, chrysin stops glycolysis
mt-ATP↓, chrysin inhibits complex II and ATPases in the mitochondria of cancer cells
Ki-67↓, the amounts of Ki-67, which is a sign of growth, and c-Myc in the tumor tissues went down
cMyc↓,
ROCK1↓, (ROCK1), transgelin 2 (TAGLN2), and FCH and Mu domain containing endocytic adaptor 2 (FCHO2) were much lower.
TOP1↓, DNA topoisomerases and histone deacetylase were inhibited, along with the synthesis of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and (IL-1 beta), while the activity of protective signaling pathways was increased
TNF-α↓,
IL1β↓,
CycB/CCNB1↓, Chrysin suppressed cyclin B1 and CDK2 production in order to stop cancerous growth.
CDK2↓,
EMT↓, chrysin treatment can also stop EMT
STAT3↓, chrysin block the STAT3 and NF-B pathways, but it also greatly reduced PD-L1 production both in vivo and in vitro.
PD-L1↓,
IL2↑, chrysin increases both the rate of T cell growth and the amount of IL-2

1033-

CHr,

Chrysin inhibits hepatocellular carcinoma progression through suppressing programmed death ligand 1 expression

vitro+vivo,

HCC,

 H22 xenograft mouse model

TumCG↓,
CD4+↑, enhanced CD4/CD8-
CD8+↑, enhanced CD4/CD8-
PD-L1↓, chrysin significantly down-regulated the expression of PD-L1 in vivo and in vitro

6203-

Cuc,

immuno,

Isocucurbitacin B targets STAT3 to induce ferroptosis and promote anti-PD1 immunotherapy responses in breast cancer

in-vitro,

BC,

MDA-MB-231

4T1 syngeneic murine mode

in-vitro,

BC,

BT549

in-vivo,

BC,

4T1

Ferroptosis↑, IB shows considerable potential as a dual-functional agent in breast cancer treatment by targeting both ferroptosis induction and STAT3 inhibition.
STAT3↓,
GPx4↓, Isocucurbitacin B (IB) targets STAT3 to induce ferroptosis through down-regulating the STAT3/SLC7A11/GPX4 axis.
Imm↑, IB attenuates immunosuppressive tumor microenvironment via inhibiting STAT3/PD-L1/PD-1 axis.
PD-L1↓,
TumCG↓, IB inhibits breast cancer tumor growth in vivo
ATP↓, depleted intracellular ATP pools
OXPHOS↓, mitochondrial metabolic assay indicated that IB reduced the level of OXPHOS,

451-

CUR,

The effect of Curcumin on multi-level immune checkpoint blockade and T cell dysfunction in head and neck cancer

vitro+vivo,

HNSCC,

SCC15

1, 2, 5, 10, 20, 40 and 80 µM, 1, 3, 6, 12 and 24 h; 50 mg/kg, 6 weeks

vitro+vivo,

HNSCC,

SNU1076

vitro+vivo,

HNSCC,

SNU1041

TumCMig↓,
TumCG↓,
PD-L1↓,
PD-L2↓,
Galectin-9↓,
EMT↓,
T-Cell↑,
TILs↑,
PD-1↓,
TIM-3↓,
CD4+↓,
CD25+↓,
FoxP3+↓,
E-cadherin↑,
CD8+↑,
IFN-γ↑,

1035-

DHA,

Docosahexaenoic acid reverses PD-L1-mediated immune suppression by accelerating its ubiquitin-proteasome degradation

vitro+vivo,

NA,

PD-L1↓, (DHA) reduced the expression of PD-L1 in cancer cells both in vitro and in vivo.
FASN↓,

1605-

EA,

Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence

Review,

Var,

*BioAv↓, Within the gastrointestinal tract, EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility.
antiOx↓, strong antioxidant properties [12,13], anti-inflammatory effects
Inflam↓,
TumCP↓, numerous studies indicate that EA possesses properties that can inhibit cell proliferation
TumCCA↑, achieved this by causing cell cycle arrest at the G1 phase
cycD1/CCND1↓, reduction of cyclin D1 and E levels, as well as to the upregulation of p53 and p21 proteins
cycE/CCNE↓,
P53↑,
P21↑,
COX2/PTGS2↓, notable reduction in the protein expression of COX-2 and NF-κB as a result of this treatment
NF-kB↓,
Akt↑, suppressing Akt and Notch signaling pathways
NOTCH↓,
CDK2↓,
CDK6↓,
JAK↓, suppression of the JAK/STAT3 pathway
STAT3↓,
EGFR↓, decreased expression of epidermal growth factor receptor (EGFR)
p‑ERK↓, downregulated the expression of phosphorylated ERK1/2, AKT, and STAT3
p‑Akt↓,
p‑STAT3↓,
TGF-β↓, downregulation of the TGF-β/Smad3
SMAD3↓,
CDK6↓, EA demonstrated the capacity to bind to CDK6 and effectively inhibit its activity
Wnt/(β-catenin)↓, ability of EA to inhibit phosphorylation of EGFR
Myc↓, Myc, cyclin D1, and survivin, exhibited decreased levels
survivin↓,
CDK8↓, diminished CDK8 level
PKCδ↓, EA has demonstrated a notable downregulatory impact on the expression of classical isoenzymes of the PKC family (PKCα, PKCβ, and PKCγ).
tumCV↓, EA decreased cell viability
RadioS↑, further intensified when EA was combined with gamma irradiation.
eff↑, EA additionally potentiated the impact of quercetin in promoting the phosphorylation of p53 at Ser 15 and increasing p21 protein levels in the human leukemia cell line (MOLT-4)
MDM2↓, finding points to the ability of reduced MDM2 levels
XIAP↓, downregulation of X-linked inhibitor of apoptosis protein (XIAP).
p‑RB1↓, EA exerted a decrease in phosphorylation of pRB
PTEN↑, EA enhances the protein phosphatase activity of PTEN in melanoma cells (B16F10)
p‑FAK↓, reduced phosphorylation of focal adhesion kinase (FAK)
Bax:Bcl2↑, EA significantly increases the Bax/Bcl-2 rati
Bcl-xL↓, downregulates Bcl-xL and Mcl-1
Mcl-1↓,
PUMA↑, EA also increases the expression of Bcl-2 inhibitory proapoptotic proteins PUMA and Noxa in prostate cancer cells
NOXA↑,
MMP↓, addition to the reduction in MMP, the release of cytochrome c into the cytosol occurs in pancreatic cancer cells
Cyt‑c↑,
ROS↑, induction of ROS production
Ca+2↝, changes in intracellular calcium concentration, leading to increased levels of EndoG, Smac/DIABLO, AIF, cytochrome c, and APAF1 in the cytosol
Endoglin↑,
Diablo↑,
AIF↑,
iNOS↓, decreased expression of Bcl-2, NF-кB, and iNOS were observed after exposure to EA at concentrations of 15 and 30 µg/mL
Casp9↑, increase in caspase 9 activity in EA-treated pancreatic cancer cells PANC-1
Casp3↑, EA-induced caspase 3 activation and PARP cleavage in a dose-dependent manner (10–100 µmol/L)
cl‑PARP↑,
RadioS↑, EA sensitizes and reduces the resistance of breast cancer MCF-7 cells to apoptosis induced by γ-radiation
Hif1a↓, EA reduced the expression of HIF-1α
HO-1↓, EA significantly reduced the levels of two isoforms of this enzyme, HO-1, and HO-2, and increased the levels of sEH (Soluble epoxide hydrolase) in LnCap
HO-2↓,
SIRT1↓, EA-induced apoptosis was associated with reduced expression of HuR and Sirt1
selectivity↑, A significant advantage of EA as a potential chemopreventive, anti-tumor, or adjuvant therapeutic agent in cancer treatment is its relative selectivity
Dose∅, EA significantly reduced the viability of cancer cells at a concentration of 10 µmol/L, while in healthy cells, this effect was observed only at a concentration of 200 µmol/L
NHE1↓, EA had the capacity to regulate cytosolic pH by downregulating the expression of the Na+/H+ exchanger (NHE1)
Glycolysis↓, led to intracellular acidification with subsequent impairment of glycolysis
GlucoseCon↓, associated with a decrease in the cellular uptake of glucose
lactateProd↓, notable reduction in lactate levels in supernatant
PDK1 / PDPK1?, inhibit pyruvate dehydrogenase kinase (PDK) -bind and inhibit PDK3
PDK1 / PDPK1?,
ECAR↝, EA has been shown to influence extracellular acidosis
COX1↓, downregulation of cancer-related genes, including COX1, COX2, snail, twist1, and c-Myc.
Snail↓,
Twist↓,
cMyc↓,
Telomerase↓, EA, might dose-dependently inhibit telomerase activity
angioG↓, EA may inhibit angiogenesis
MMP2↓, EA demonstrated a notable reduction in the secretion of matrix metalloproteinase (MMP)-2 and MMP-9.
MMP9↓,
VEGF↓, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
Dose↝, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
PD-L1↓, EA downregulated the expression of the immune checkpoint PD-L1 in tumor cells
eff↑, EA might potentially enhance the efficacy of anti-PD-L1 treatment
SIRT6↑, EA exhibited statistically significant upregulation of sirtuin 6 at the protein level in Caco2 cells
DNAdam↓, increase in DNA damage

1037-

EA,

Unripe Black Raspberry (Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction

in-vivo,

CRC,

25 to100 μg/mL

83.8 ± 4.7 μg/mL

humanized PD-1 mice bearing MC38 colorectal tumor

AntiTum↑, potent anti-tumor activity similar to anti-PD-1 antibody.
PD-L1↓, potent anti-tumor effect via PD-1/PD-L1 blockade

1036-

EGCG,

Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth

in-vitro,

Lung,

A549

10 and 50 µM

in-vitro,

Lung,

LU99

PD-L1↓, 50 µM EGCG decreased PD-L1 mRNA by 86% (from 5.8-fold to 0.8-fold) and PD-L1 protein by 79%
EGF↓,
Akt↓,

1022-

EVO,

Evodiamine suppresses non-small cell lung cancer by elevating CD8+ T cells and downregulating the MUC1-C/PD-L1 axis

in-vivo,

Lung,

H1975

Female H1975 xenograft nude mice

in-vitro,

Lung,

H1650

TumCG↓,
Apoptosis↑,
TumCCA↑, cell cycle arrest at G2 phase
PD-L1↓,
MUC1-C↓,
TumVol↓, reduced tumor size

1039-

Fuc,

Anti-Proliferative and Pro-Apoptotic vLMW Fucoidan Formulas Decrease PD-L1 Surface Expression in EBV Latency III and DLBCL Tumoral B-Cells by Decreasing Actin Network

in-vitro,

NA,

TumCP↓, no toxicity on normal B- and T-cells.
Apoptosis↑,
PD-L1↓, We highlighted a decrease in transcriptional and PD-L1 surface expression, even more efficient for vLMW than native fucoidan.

997-

GA,

The Inhibitory Mechanisms of Tumor PD-L1 Expression by Natural Bioactive Gallic Acid in Non-Small-Cell Lung Cancer (NSCLC) Cells

in-vitro,

Lung,

A549

400 μM @48hrs

in-vitro,

Lung,

H292

100 μM@48hrs

in-vitro,

Nor,

HUVECs

400 μM GA inducing around 8% cell death which indicated that this concentration does not make much toxicity in normal cells  ****

PD-L1↓, GA strongly decreases the expression levels of PD-L1 protein in A549 and H292 NSCLC cells
p‑EGFR↓,
p‑PI3K↓,
p‑Akt↓,
P53↑, GA upregulates the expression levels of p53 protein in a concentration-dependent manner
miR-34a↑, p53 indirectly regulates the expression levels of PD-L1 through inducing miR-34a in cancer cells
*toxicity↓, 400 μM GA inducing around 8% cell death which indicated that this concentration does not make much toxicity in normal cells

1021-

HNK,

Honokiol suppress the PD-L1 expression to improve anti-tumor immunity in lung cancer

in-vivo,

Lung,

PD-L1↓, in cells with high PD-L1 expression
T-Cell↑, facilitates T cell killing of tumor cells
CD4+↑,
CD8+↑,
TumCG↓, mice

1004-

HNK,

RAPA,

PD-L1_expression_and_enhances_antitumor_effects_of_mTOR_inhibitors_in_renal_cancer_cells">Honokiol downregulates PD-L1 expression and enhances antitumor effects of mTOR inhibitors in renal cancer cells

in-vitro,

RCC,

Apoptosis↑, HNK is more potent than RAPA, both HNK and RAPA inhibited the proliferation of renal cancer cells and promoted apoptosis
TumCCA↑, G1 phase cell cycle arrest
ROS↑, HNK and RAPA significantly increased ROS generation in these cells and it was much higher in the HNK and RAPA combinatorial treatment.
PD-L1↓, HNK, but not RAPA, significantly decreased the expression of PD-L1
IFN-γ↓, HNK can also downmodulate IFN-γ-induced PD-L1expression

7567-

HYP,

Hyperoside: A review on its sources, biological activities, and molecular mechanisms

Review,

Var,

*AntiCan↑, anticancer, anti-inflammatory, antibacterial, antiviral, antidepressant, and organ protective effects.
*Bacteria↓,
*AntiViral↑,
*antiD↓,
*RenoP↑, Kidney protection
*hepatoP↑, Liver protection
*eff↑, treating multiple diseases, such as sepsis, arthritis, colitis, diabetic nephropathy, myocardial ischemia-reperfusion, pulmonary fibrosis, and cancers.
*Sepsis↓,
*AntiArt↑,
*Stroke↓,
TumCMig↓, hyperoside has been shown to inhibit the migration and invasion properties of A549 cells by suppressing the expression of metastasis-associated gene 1 (MTA1), matrix metalloproteinase-2 inhibitor (TIMP-2), matrix metalloproteinase (MMP)-2
TumCI↓,
MTA1↓,
TIMP2↓,
MMP2↓,
MMP↓, disrupted the penetration of the mitochondrial membrane, and triggered mitochondrial cytochrome C and apoptosis inducers into the cytoplasm
Cyt‑c↑,
Akt↓, inhibited the Akt/mTOR/p70S6K signaling pathway in NSCLC cells to promote autophagy and exerted anticancer activity
mTOR↓,
P70S6K↓,
TumAuto↑,
PD-L1↓, thereby inhibiting PD-L1 expression at the transcriptional leve
TNF-α↓, subsequently, inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1b, IL-6 and IL-8, were significantly down-regulated
IL1β↓,
IL6↓,
IL8↓,
Bcl-2↓, Hyperoside was reported to inhibit the over-expression of B-cell lymphoma factor 2 (Bcl)-2 and Bcl-x in lung cancer cells, and up-regulate the preapoptotic factors such as Bax, Bad, and Bak.
Bcl-xL↓,
BAX↑,
BAD↑,
Bak↑,
VEGF↓, decreasing the HeLa cell's vascular endothelial growth factor (VEGF) expression levels in HeLa cells.
Casp3↑, hyperoside promoted apoptosis via enhancing caspase-3 and caspase-8 protein expression, and on the other hand, by promoting tumor suppressor gene P35 expression
Casp8↑,
P53↑,
GSH↓, Hyperoside could also reduce glutathione levels in HeLa cells, superoxide dismutase (SOD), and Catalase (CAT) viability.
SOD↓,
Catalase↓,
TAC↓, reduced the antioxidant capacity and thus to inhibit cancer cell growth
XIAP↓, MCF-7 and 4 T1 cells Decreased the levels of Bcl-2 and XIAP; increased the levels of Bax and cleaved cysteine protease-3; decreased the production of ROS and inhibited NFκB signal pathway
ROS↓,
NF-kB↓,
TLR4↓, MDA-MB-231 cells Inhibited TLR4-NF-κB signaling pathways; decreased the expression of Bcl-2; enhanced the expression of pro-apoptotic Bax and the level of pro-inflammatory cytokine IL-6
P-gp/ABCB1↓, S180 cancer cell Reduced the expression of P-gp, LRP and Bcl-2 and increased the expression of Fas; inhibited bad phosphorylation and increased p27 level
LRP1↓,
Fas↑,
p27/CDKN1B↑,
*cardioP↑, Cardiovascular protection In vivo pulmonary embolism and arterial thrombosis model Prolonged the activated prothrombin time and suppressed thrombin and FXa activities; inhibit the production of PAI-1 induced by TNF-α
*AntiThr↑,
*PAI-1/SERPINE1↓,
*BUN↓, Reduced the contents of serum angiotensin converting enzyme ArgII, ALD, U-mAlb, BUN, SCR, ALT, and AST
*ALAT↓,
*AST↓,
*neuroP?, Neuroprotection

8235-

LCA,

Anticancer effects of licochalcones: A review of the mechanisms

Review,

Var,

mt-Apoptosis↑, licochalcones can activate the mitochondrial apoptosis pathway and the death receptor pathway, promote autophagy-related protein expression, inhibit cell cycle protein expression,
TumAuto↑,
TumCMig↓, regulate cancer migration-related protein expression via multiple signaling pathways, including EGFR/ERK, PI3K/Akt/mTOR, p38/JNK, JAK2/STAT3, MEK/ERK, Wnt/β-catenin, and MKK4/JNK signaling pathways.
LC3‑Ⅱ/LC3‑Ⅰ↑, increasing the LC3-II/LC3-I ratio, as well as the levels of the autophagy-related proteins ATG5, ATG7, and P62.
ATG5↑,
ATG7↑,
p62↑,
CHOP/DDIT3↑, LA-induced increases in CHOP expression also promote autophagy
ER Stress↑, LA-induced autophagy in lung cancer cells is associated with the induction of endoplasmic reticulum stress
UPR↑, LA (10 μM) enhances the expression of miR-144-3p, causes unfolded protein response,
ATG3↑, triggers autophagy by promoting the accumulation and expression of ATG1, ATG3, ATG6, and ATG16 via activation of the PERK/ATF4/CHOP signaling pathway
Beclin-1/ATG6↑,
ATG16L1↑,
PERK↑,
ATF4↑,
ATP↓, LA (2.5–25 μM) inhibited ATP production and caused mitochondrial dysfunction in H1299 and H322 lung cancer cells by inhibiting hypoxia-induced HIF-1α accumulation and the expression of target genes GLUT1 and PDK1
Hif1a↓,
GLUT1↓,
PDK1 / PDPK1↓,
Bcl-xL↓, induce apoptosis in H460 and A549 lung cancer cells by decreasing the levels of Bcl-xL and Bcl-2 while increasing the levels of Bad, Bax, cleaved PARP, and caspase-3
Bcl-2↓,
BAD↑,
BAX↑,
Casp3↑,
survivin↓, LA (5–50 μM) downregulated the expression of survivin by inhibiting the EGFR signaling pathway and its downstream kinases ERK1/2 and AKT in H3255, HCC827, H1975, and A549 lung cancer cells
EGFR↓,
ERK↓,
Akt↓,
mtDam↑, LB (5–15 μM) inhibited the EGFR and MET signaling pathways and induced mitochondrial dysfunction and endoplasmic reticulum stress in HCC827 lung cancer cells, which induced the loss of MMP, release of cytochrome c, and increased expression of casp
MMP↓,
Cyt‑c↑,
Casp↑,
MDM2↓, By inhibiting the expression of MDM2, cyclin B1, CDC2, and CDC25C, LA (10–15 μM) led to cell cycle arrest of H460 and A549 lung cancer cells at the G2/M phase
CycB/CCNB1↓,
CDC2↓,
CDC25↓,
TumCCA↑,
TumCP↓, decreases in the proliferation of lung cancer cells by LA were related to the inhibition of the Wnt/β-catenin signaling pathway
Wnt↓,
β-catenin/ZEB1↓,
Sp1/3/4↓, LA (2–20 μM) inhibited the AKT signaling pathway and the expression of the downstream transcription factor Sp1, which reduced the levels of MMP-1 and MMP-3 and inhibited the migration and invasion of A549 and H460 lung cancer cells
MMP-10↓,
MMP3↓,
TumCI↓,
Imm↑, Activation of the immune system
PD-L1↓, LA (10–50 μM) inhibited the expression of PD-L1 and thereby induced the production of reactive oxygen species (ROS) in A549 lung cancer cells, which inhibited the phosphorylation of 4EBP1, activated the PERK/eIF2α pathway,
ROS↑,
4E-BP1↓,
eIF2α↓,
PI3K↓, By inhibiting the PI3K/Akt/mTOR signaling pathway, LA (5–20 μM) activated the mitochondrial apoptosis pathway
mTOR↓,
p‑cMET↑, LA (1–50 μM) induced endoplasmic reticulum stress in HepG2 cells by inducing phosphorylation of VEGFR2, c-Met receptor, and PLCγ1 and enhancing the cytosolic Ca2+ release from the endoplasmic reticulum, which subsequently induced ROS accumulation
Ca+2↑,
RUBCN↓, LA-induced (5–50 μM) downregulation of PDK1 and rubicon by activating the ULK1/Atg13 signaling pathway and increasing the expression of TSC1/2, PRAS40, CTMP, and PP2A.
ATG13↑,
TSC1↑,
TSC2↑,
PRAS40↑,
PP2A↑,
ULK1/ATG1↑,
THEM4/CTMP↑,
DR5↑, LA activates the death receptor pathway and caspase cascade by increasing the expression of DR3, DR5, and Fas.
Fas↑,
TNFRSF25/DR3/APO3/LARD/TRAMP/WSL1↑,
PKCδ↓, LA also decreases the expression of the survival factor PKCε, p70S6K, and Akt.
P70S6K↓,
VEGF↓, Via downregulation of VEGF-A, LE (7–14 mg/kg) inhibited angiogenesis in cancer tissue in a xenograft mouse model using MDA-MB 231 breast cancer cells
angioG↓,
HK2↓, Moreover, the inhibitory effect of LA (10–50 μM) on the AKT signaling pathway can downregulate the expression of hexokinase 2A and inhibit glycolysis, thereby inducing apoptosis of MKN45 and SGC7901 cells
Glycolysis↓,
TrxR1↓, LA (10–40 μM) can enhance the production of intracellular ROS by inhibiting the expression of thioredoxin reductase-1, which activates the mitochondrial apoptosis pathway and induces apoptosis in HCT-116 cells
APAF1↑, By increasing intracellular Ca2+ and ROS levels, decreasing mitochondrial membrane potential, upregulating Apaf-1, caspase-9, caspase-3, and cleaved PARP levels, and elevating the Bax/Bcl-2 ratio, LA (10–80 μM) induced T24 cells apoptosis
cl‑PARP↑,
Bax:Bcl2↑,
ABCG2↓, By reducing the expression of BCRP, LA (10–100 μM) reduced the BCRP-mediated efflux of doxorubicin and temozolomide in BCRP-MDCKII cells.
BioEnh↑, Inhibition of BCRP expression can promote increased intestinal (re)uptake of antineoplastic drugs and decrease their hepatic metabolization, thereby enhancing their bioavailability.

8237-

LCA,

Role of Licochalcone A in Potential Pharmacological Therapy: A Review

Review,

Var,

*other↝, Licorice always functions as an adjuvant drug in traditional Chinese medicine to reduce the toxicity of other medicinal herbs or enhance their pharmacological effects.
*Inflam↓, LA demonstrates various pharmacological properties, including anti-inflammation, antibacterial, antioxidant, anti-parasitic, bone protection, neuroprotection, skin protection, and blood glucose and lipid regulation.
*Bacteria↓,
*antiOx↑,
*AntiP↑,
*neuroP↑,
*glucose↝,
*lipid-P↓,
PKCδ↓, Downregulation of PKCε, p70S6K, and Akt is also described
P70S6K↓,
Akt↓,
ER Stress↑, LA induced ER stress in HepG2 cells to induce apoptosis
Apoptosis↑,
Ca+2↑, enhancing cytosolic Ca2+ release from the ER
PI3K↓, apoptosis of MCF-7 by inhibiting PI3K-Akt-mTOR signaling, thereby increasing caspase-3 activity, decreasing expression of B-cell lymphoma-2, and triggering the release of cytochrome from mitochondria into the cytoplasm
mTOR↓,
Casp3↑,
Bcl-2↓,
Cyt‑c↑,
BAX↑, upregulation of Bax expression and PARP cleavage, downregulation of Bcl-2 and Cyclin D1, and accumulation of reactive oxygen species (ROS)
cl‑PARP↑,
cycD1/CCND1↑,
ROS↑,
CHOP/DDIT3↑, CHOP expression was elevated in parallel
ERK↑, LA significantly activated ERK and p38 in A549 and H460 cells in a time-dependent manner.
p38↑,
JNK↓, LA also inhibited the activity of JNK, suppressed the expression of c-IAP1, c-IAP2, XIAP, Survivin, c-FLIPL, and RIP1, and attenuated LA-induced induction of autophagy
IAP1↓,
XIAP↓,
survivin↓,
cFLIP↓,
RIP1↓,
EGFR↓, promoted the degradation of EGFR, Met, Her2
MET↓,
HER2/EBBR2↓,
p‑4E-BP1↓, LA may inhibit the phosphorylation of 4EBP1 (Ser 65) and activate the PERK-eIF2α pathway to inhibit PD-L1 translation
PERK↑,
eIF2α↑,
PD-L1↓,
HK2↓, Hexokinase 2Â (HK2) expression was downregulated at a lower dose, attenuating glycolysis elevation and inducing apoptosis in MKN-45 and SGC7901 cells
Glycolysis↓,
Sp1/3/4↓, LA induced apoptosis via downregulating the expression of specificity protein 1 (Sp1), upregulating Bax, Bid, Bcl-xl, caspase-3, and PARP cleavage with doses of 10–40 μM
FasL↑, LA induced apoptosis in KB cells, relying on activation of caspase-dependent factor associated suicide ligand (FasL) mediated death receptor pathway.
MMP↓, reducing mitochondrial membrane potential and inhibiting ATP production in vitro
ATP↓,
TumAuto↑, The literature also showed that LA induced apoptosis and autophagy in SiHa
WEE1↑, LA blocked the cell cycle in HepG2 cells by increasing the expression of Weel, P21, Cyclin D1, and JNK1 and decreasing the expression of Survivin, Cyclin B1, and CDK1 using doses of 30–70 μM
P21↑,
CDK1↓,
TumCCA↑,
TumCMig↓, LA exhibited the ability to inhibit migration and invasion of A549 and H460 cells at relatively lower doses (2–20 μM)
TumCI↓,
ABCG2↓, downregulating the expression of breast cancer resistance protein (BCRP)
HSP90↓, LA also reduced Hsp90 activity in gefitinib-resistant NSCLC cells (H1975) via binding to the N-terminal ATP binding site of Hsp90 to reduce drug resistance
T-Cell↑, LA (40 mg/kg) to C3H/HeN mice bearing UM-UC-3 cells enhanced the activity of cytotoxic T lymphocytes and counts of CD4+ CD25+ Foxp3+ T regulatory T cells. Thus, LA might treat bladder cancer by modulating the tumor immune microenvironment
CD4+↑,
CD25+↑,
FOXP3↑,
Imm↝,
*Inflam↓, LA demonstrates anti-inflammatory activity via interaction with MAPK, NF-κB, NLRP3, and Nrf2 signaling in the acute lung, kidney, and liver injury (acute inflammation) and arthritis and asthma
*NF-kB↓,
*NRF2↑,
*AntiArt↑,

8212-

LCA,

Licochalcone A inhibits proliferation and promotes apoptosis of colon cancer cell by targeting programmed cell death-ligand 1 via the NF-κB and Ras/Raf/MEK pathways

in-vitro,

Colon,

HepG3

in-vitro,

Lung,

A549

in-vitro,

Cerv,

HeLa

vitro+vivo,

CRC,

HCT116

mice

PD-L1↓, we found that licochalcone A suppressed the expression of programmed cell death ligand-1 (PD-L1), which plays a key role in regulating the immune response.
p65↓, licochalcone A inhibited the expressions of p65 and Ras.
RAS?,
NF-kB↓, Licochalcone A (LCA) inhibits TNF-α induced NF-κB signaling pathways activation in HCT116 cells
T-Cell↑, The results showed that licochalcone A (LCA) significantly enhanced the killing of T cells to HCT116 cell
p‑MEK↓, Licochalcone A (LCA) also inhibited TNF-α-induced p-MEK and p-Raf expressions without affecting MEK and Raf total protein levels
p‑Raf↓,

1025-

LT,

Api,

Luteolin and its derivative apigenin suppress the inducible PD-L1 expression to improve anti-tumor immunity in KRAS-mutant lung cancer

in-vivo,

Lung,

H358 xenograft and Lewis lung carcinoma model in vivo,

TumCG↓,
Apoptosis↑,
PD-L1↓, down-regulated the IFN-γ-induced PD-L1 expression
p‑STAT3↓,

1042-

MEL,

Melatonin Downregulates PD-L1 Expression and Modulates Tumor Immunity in KRAS-Mutant Non-Small Cell Lung Cancer

in-vitro,

Lung,

A549

in-vitro,

Lung,

H460

in-vitro,

Lung,

LLC1

PD-L1↓, we found that lung cancer cells harboring the KRAS mutation exhibited a higher level of programmed death ligand 1 (PD-L1). However, treatment with melatonin substantially downregulated PD-L1
YAP/TEAD↓,
TAZ↓,
TumCG↓, mouse

1043-

MET,

immuno,

Metformin reduces PD-L1 on tumor cells and enhances the anti-tumor immune response generated by vaccine immunotherapy

in-vitro,

NA,

eff↑, metformin can synergize with vaccine immunotherapy to augment the antitumor response
PD-L1↓, Metformin reduces PD-L1 on tumor cells
Ki-67↑, While these effector CD8 T cells have better cytotoxic capabilities,40 the central memory phenotype has better proliferative capabilities, as we observed an increase in Ki-67 expression
TIM-3↑,
L-sel↑,

1044-

Myr,

Myricetin inhibits interferon-γ-induced PD-L1 and IDO1 expression in lung cancer cells

in-vitro,

Lung,

PD-L1↓,
IDO1↓,

5603-

NaHCO3,

immuno,

Acidosis-mediated increase in IFN-γ-induced PD-L1 expression on cancer cells as an immune escape mechanism in solid tumors

in-vitro,

BC,

MCF7

in-vitro,

PC,

MIA PaCa-2

in-vitro,

GBM,

U87MG

eff↑, These findings have important implications for the development of new strategies to enhance the efficacy of immunotherapy in cancer patients.
e-pH↑, In vivo studies fully validated our in vitro findings and revealed that neutralizing the acidic extracellular tumor pH by sodium bicarbonate treatment suppresses IFN-γ-induced PD-L1 expression and promotes immune cell infiltration in responsive tumor
PD-L1↓,

5602-

NaHCO3,

immuno,

Immunotherapy Enhancement by Targeting Extracellular Tumor pH in Triple-Negative Breast Cancer Mouse Model

in-vivo,

BC,

4T1

mouse

eff↑, n this study, oral administration of either sodium bicarbonate or sodium bicarbonate plus anti-PD-L1 combination enhanced responses to anti-tumor immunity by tumor growth inhibition and improving survival time in TNBC.
TumCG↓,
OS↑,
e-pH↑, Here, we show that NaHCO3 increased extracellular pH (pHe) in tumor tissues in vivo
IFN-γ↑, an effect that was accompanied by an increase in T cell infiltration, T cell activation and IFN-γ, IL2 and IL12p40 mRNA expression in tumor tissues
IL2↑, The expression of IFN-γ, IL-2 and IL-12 mRNA was significantly increased in response to NaHCO3 alone
IL12↑,
Dose↝, The mice in group number three were given drinking water with 200 mM NaHCO3 to increase the pHe > 7.2 via bicarbonate-induced metabolic alkalosis
PD-L1↓, Sodium Bicarbonate Therapy Decreases Tumor PD-L1 Expression In Vivo

5254-

NCL,

The magic bullet: Niclosamide

Review,

Var,

Wnt↓, In particular, niclosamide inhibits multiple oncogenic pathways such as Wnt/β-catenin, Ras, Stat3, Notch, E2F-Myc, NF-κB, and mTOR and activates tumor suppressor signaling pathways such as p53, PP2A, and AMPK.
β-catenin/ZEB1↓,
RAS↓,
STAT3↓,
NOTCH↓,
E2Fs↓,
mTOR↓,
eff↑, Moreover, niclosamide potentially improves immunotherapy by modulating pathways such as PD-1/PDL-1.
PD-1↓,
PD-L1↓, primarily through PD-L1 ligand downregulation in cancer cells.
BioAv↝, The original pharmacokinetics study showed that the maximal serum concentration can reach 0.25-6.0ug/ml (0.76-18.34 µM) following administration of a single 2g dose (11).
toxicity↓, a strong safety profile and tolerability in humans.
BioAv↑, A potential solution to the aforementioned challenge is niclosamide ethanolamine (NEN), a salt form of niclosamide that also functions as a mitochondrial uncoupler with a superior safety profile and enhanced bioavailability
ETC↑, NEN activates the ETC to boost NADH oxidation, thereby leading to an increased intracellular NAD+/NADH ratio and driving the TCA cycle forward.
NADH:NAD↓,
TCA↑,
Warburg↓, leading to a reversal of the Warburg effect and the induction of cellular differentiation
Diff↑,
AMPK↑, figure 3
P53↑,
PP2A↑,
HIF-1↓,
KRAS↓,
Myc↓,
RadioS↑, leading to a reversal of the Warburg effect and the induction of cellular differentiation
ChemoSen↑, Niclosamide has shown synergistic anti-tumor effects with a broad spectrum of chemotherapy drugs.
Dose↝, In this trial, either 500mg or 1000mg niclosamide was given three times daily to patients. However, the maximal plasma concentration ranged from 35.7–82 ng/mL (0.1µM-0.25 µM), a range that failed to be consistently above the minimum effective concent
Dose↑, In contrast, the ongoing clinical trial NCT02807805 is administering 1200 mg of reformulated orally bioavailable niclosamide orally (PO) three times daily to patients, resulting in 0.21µM-0.723 plasma niclosamide concentrations exceeding the therape

1045-

OLST,

Fatty acid synthase inhibitor orlistat impairs cell growth and down-regulates PD-L1 expression of a human T-cell leukemia line

in-vitro,

AML,

Jurkat

FASN↓,
TumCG↓,
PD-L1↓, remarkable impairment of PD-L1 expression

1813-

Oxy,

Advances in hyperbaric oxygen to promote immunotherapy through modulation of the tumor microenvironment

Review,

Var,

ChemoSen↑, HBO can reduce drug resistance to chemotherapy and radiotherapy
RadioS↑,
PD-L1↓, HBO promotes immunotherapy by relieving tissue hypoxia and down-regulating PD-L1
Hif1a↓, HBO can inhibit HIF1α in tumors
ROS↑, Hyperbaric oxygen produces ROS

1048-

RosA,

GSL,

Rosmarinic acid in combination with ginsenoside Rg1 suppresses colon cancer metastasis via co-inhition of COX-2 and PD1/PD-L1 signaling axis

in-vivo,

Colon,

MC38

RA (50, 100, 150 μM)

mice

TumCMig↓,
TumCI↓,
PD-1↓, RA in combination with GR that had inhibitory effect on the binding of PD-1 and PD-L1
COX2/PTGS2↓,
PD-L1↓,

Showing Research Papers: 1 to 50 of 60
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 60

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome(tgid=24) ⓘ

CD8+↑, 3, Sepsis↓, 1,
Total Targets: 312

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

AntiArt↑, 2, antiD↓, 1, AntiP↑, 1, Stroke↓, 1,

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 2, Catalase↑, 2, GPx↑, 2, GSH↑, 1, GSTs↑, 1, HO-1↓, 1, lipid-P↓, 2, MDA↓, 2, NRF2↑, 2, ROS↓, 3, SOD↑, 3, TAC↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1, BUN↓, 1, glucose↝, 1,

Cell Death(tgid=5) ⓘ

Casp3↓, 1,

Transcription & Epigenetics(tgid=7) ⓘ

AntiThr↑, 1, other↝, 1,

Migration(tgid=13) ⓘ

PAI-1/SERPINE1↓, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 4, NF-kB↓, 2, TLR2↓, 1,

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1, eff↑, 3,

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1, AST↓, 1,

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1, cardioP↑, 1, chemoP↑, 1, cognitive↓, 1, hepatoP↑, 2, neuroP?, 1, neuroP↑, 2, RenoP↑, 1, toxicity↓, 2,

Infection & Microbiome(tgid=24) ⓘ

AntiViral↑, 1, Bacteria↓, 2, Sepsis↓, 1,
Total Targets: 43

Scientific Paper Hit Count for: PD-L1, Programmed Death-Ligand 1

7 immunotherapy
5 Baicalein
4 Thymoquinone
3 Astragalus
3 Chrysin
3 Licochalcone A
3 Silymarin (Milk Thistle) silibinin
2 Apigenin (mainly Parsley)
2 Curcumin
2 Aspirin
2 beta-glucans
2 Baicalin
2 Chlorogenic acid
2 Ellagic acid
2 Honokiol
2 Bicarbonate(Sodium)
1 Silver-NanoParticles
1 Allicin (mainly Garlic)
1 Artemisinin
1 Berberine
1 Biochanin A
1 Butyrate
1 Capsaicin
1 Trastuzumab
1 Propolis -bee glue
1 Cucurbitacin
1 Docosahexaenoic Acid
1 EGCG (Epigallocatechin Gallate)
1 Evodiamine
1 Fucoidan
1 Gallic acid
1 Rapamycin
1 Hyperoside
1 Luteolin
1 Melatonin
1 Metformin
1 Myricetin
1 Niclosamide (Niclocide)
1 Orlistat
1 Oxygen, Hyperbaric
1 Rosmarinic acid
1 Germacranolide sesquiterpene lactone
1 Shikonin
1 Usnic acid
1 Vitamin C (Ascorbic Acid)

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:243  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

PD-L1 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Cellular Microenvironment(tgid=17) ⓘ

Protein Aggregation(tgid=19) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Migration(tgid=13) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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