MMP3 Cancer Research Results
MMP3, Matrix metalloproteinase-3: Click to Expand ⟱
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MP-3: also known as stromelysin-1, is a type of enzyme that plays a crucial role in the degradation of the extracellular matrix (ECM).
MMP-3 can break down the ECM, allowing cancer cells to invade surrounding tissues and form new tumors.
High levels of MMP-3 expression are associated with poor prognosis in various types of cancer, including breast, lung, and colon cancer.
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Scientific Papers found: Click to Expand⟱
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Inflam↓, anti-inflammatory, antidiabetic, antibacterial, antiparasitic, antidiarrheal, antihypertensive, hypolipidemic, and fungicide.
AntiCan↑, elaborated on the anticancer effects of BBR through the regulation of different molecular pathways such as: inducing apoptosis, autophagy, arresting cell cycle, and inhibiting metastasis and invasion.
Apoptosis↑,
TumAuto↑,
TumCCA↑,
TumMeta↓,
TumCI↓,
eff↑, BBR is shown to have beneficial effects on cancer immunotherapy.
eff↑, BBR inhibited the release of Interleukin 1 beta (IL-1β), Interferon gamma (IFN-γ), Interleukin 6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) from LPS stimulated lymphocytes by acting as a dopamine receptor antagonist
CD4+↓, BBR inhibited the proliferation of CD4+ T cells and down-regulated TNF-α and IL-1 and thus, improved autoimmune neuropathy.
TNF-α↓,
IL1↓,
BioAv↓, On the other hand, P-Glycoprotein (P-gp), a secretive pump located in the epithelial cell membrane, restricts the oral bioavailability of a variety of medications, such as BBR. The use of P-gp inhibitors is a common and effective way to prevent this
BioAv↓, Regardless of its low bioavailability, BBR has shown great therapeutic efficacy in the treatment of a number of diseases.
other↓, BBR has been also used as an effective therapeutic agent for Inflammatory Bowel Disease (IBD) for several years
AMPK↑, inhibitory effects on inflammation by regulating different mechanisms such as 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK. Increase of AMPK
MAPK↓, Mitogen-Activated Protein Kinase (MAPK), and NF-κB signaling pathways
NF-kB↓,
IL6↓, inhibiting the expression of proinflammatory genes such as IL-1, IL-6, Monocyte Chemoattractant Protein 1 (MCP1), TNF-α, Prostaglandin E2 (PGE2), and Cyclooxygenase-2 (COX-2)
MCP1/CCL2↓,
PGE2↓,
COX2/PTGS2↓,
*ROS↓, BBR protected PC-12 cells (normal) from oxidative damage by suppressing ROS through PI3K/AKT/mTOR signaling pathways
*antiOx↑, BBR therapy improved the antioxidant function of mice intestinal tissue by enhancing the levels of glutathione peroxidase and catalase enzymes.
*GPx↑,
*Catalase↑,
AntiTum↑, Besides, BBR leaves great antitumor effects on multiple types of cancer such as breast cancer,69 bladder cancer,70 hepatocarcinoma,71 and colon cancer.72
TumCP↓, BBR exerts its antitumor activity by inhibiting proliferation, inducing apoptosis and autophagy, and suppressing angiogenesis and metastasis
angioG↓,
Fas↑, by increasing the amounts of Fas receptor (death receptor)/FasL (Fas ligand), ROS, ATM, p53, Retinoblastoma protein (Rb), caspase-9,8,3, TNF-α, Bcl2-associated X protein (Bax), BID
FasL↑,
ROS↑,
ATM↑,
P53↑,
RB1↑,
Casp9↑,
Casp8↑,
Casp3↓,
BAX↑,
Bcl-2↓, and declining Bcl2, Bcl-X, c-IAP1 (inhibitor of apoptosis protein), X-linked inhibitor of apoptosis protein (XIAP), and Survivin levels
Bcl-xL↓,
IAP1↓,
XIAP↓,
survivin↓,
MMP2↓, Furthermore, BBR suppressed Matrix Metalloproteinase-2 (MMP-2), and MMP-9 expression.
MMP9↓,
CycB/CCNB1↓, Inhibition of cyclin B1, cdc2, cdc25c
CDC25↓,
CDC25↓,
Cyt‑c↑, BBR inhibited tumor cell proliferation and migration and induced mitochondria-mediated apoptosis pathway in Triple Negative Breast Cancer (TNBC) by: stimulating cytochrome c release from mitochondria to cytosol
MMP↓, decreased the mitochondrial membrane potential, and enabled cytochrome c release from mitochondria to cytosol
RenoP↑, BBR significantly reduced the destructive effects of cisplatin on the kidney by inhibiting autophagy, and exerted nephroprotective effects.
mTOR↓, U87 cell, Inhibition of m-TOR signaling
MDM2↓, Downregulation of MDM2
LC3II↑, Increase of LC3-II and beclin-1
ERK↓, BBR stimulated AMPK signaling, resulting in reduced extracellular signal–regulated kinase (ERK) activity and COX-2 expression in B16F-10 lung melanoma cells
COX2/PTGS2↓,
MMP3↓, reducing MMP-3 in SGC7901 GC and AGS cells
TGF-β↓, BBR suppressed the invasion and migration of prostate cancer PC-3 cells by inhibiting TGF-β-related signaling molecules which induced Epithelial-Mesenchymal Transition (EMT) such as Bone morphogenetic protein 7 (BMP7),
EMT↑,
ROCK1↓, inhibiting metastasis-associated proteins such as ROCK1, FAK, Ras Homolog Family Member A (RhoA), NF-κB and u-PA, leading to in vitro inhibition of MMP-1 and MMP-13.
FAK↓,
RAS↓,
Rho↓,
NF-kB↓,
uPA↓,
MMP1↓,
MMP13↓,
ChemoSen↑, recent studies have indicated that it can be used in combination with chemotherapy agents
*cognitive↑, Bacopa monnieri, also known as brahmi, which has gained particular popularity for its cognitive-function-enhancing properties and neuroprotective effects.
*neuroP↑,
*PI3K↑, figure 3
*Akt↑,
*GSK‐3β↓,
*tau↓,
*ROS↓,
*MMP3↓,
*Casp1↓,
*Casp3↓,
*NF-kB↓,
*TNF-α↓,
*IL6↓,
Snail↑,
ITGB1↑,
ITGA5↑,
COL1A1↓, 50 mM 24 h of BA treatment could be more beneficial as it reduces the expression of COL1A1 in cancer stem cells.
LAMA5↑,
MMP3↓,
Vim↓,
E-cadherin↑,
EMT↓, inhibit the EMT of lung cancer stem cells by reducing E-cadherin and Collagen-1 expression.
Zeb1↑,
*5LO↓, Arthritis Human primary chondrocytes: 5-LOX↓, TNF-α↓, MMP3↓
*TNF-α↓,
*MMP3↓,
*COX1↓, COX-1↓, Leukotriene synthesis by 5-LOX↓
*COX2/PTGS2↓, Arthritis Human blood in vitro: COX-2↓, PGE2↓, TH1 cytokines↓, TH2 cytokines↑
*PGE2↓,
*Th2↑,
*Catalase↑, Ethanol-induced gastric ulcer: CAT↑, SOD↑, NO↑, PGE-2↑
*SOD↑,
*NO↑,
*PGE2↑,
*IL1β↓, inflammation Human PBMC, murine RAW264.7 macrophages: TNFα↓ IL-1β↓, IL-6↓, Th1 cytokines (IFNγ, IL-12)↓, Th2 cytokines (IL-4, IL-10)↑; iNOS↓, NO↓, phosphorylation of JNK and p38↓
*IL6↓,
*Th1 response↓,
*Th2↑,
*iNOS↓,
*NO↓,
*p‑JNK↓,
*p38↓,
GutMicro↑, colon carcinogenesis: gut microbiota; pAKT↓, GSK3β↓, cyclin D1↓
p‑Akt↓,
GSK‐3β↓,
cycD1/CCND1↓,
Akt↓, Prostate Ca: AKT and STAT3↓, stemness markers↓, androgen receptor↓, Sp1 promoter binding↓, p21(WAF1/CIP1)↑, cyclin D1↓, cyclin D2↓, DR5↑,CHOP↑, caspases-3/-8↑, PARP cleavage, NFκB↓, IKK↓, Bcl-2↓, Bcl-xL↓, caspase 3↑, DNA
STAT3↓,
CSCs↓,
AR↓,
P21↑,
DR5↑,
CHOP/DDIT3↑,
Casp3↑,
Casp8↑,
cl‑PARP↑,
DNAdam↑,
p‑RB1↓, Glioblastoma: pRB↓, FOXM1↓, PLK1↓, Aurora B/TOP2A pathway↓,CDC25C↓, pCDK1↓, cyclinB1↓, Aurora B↓, TOP2A↓, pERK-1/-2↓
FOXM1↓,
TOP2↓,
CDC25↓,
p‑CDK1↓,
p‑ERK↓,
MMP9↓, Pancreas Ca: Ki-67↓, CD31↓, COX-2↓, MMP-9↓, CXCR4↓, VEGF↓
VEGF↓,
angioG↓, Apoptosis↑, G2/M arrest, angiogenesis↓
ROS↑, ROS↑,
Cyt‑c↑, Leukemia : cytochrome c↑, AIF↑, SMAC/DIABLO↑, survivin↓, ICAD↓
AIF↑,
Diablo↑,
survivin↓,
ICAD↓,
ChemoSen↑, Breast Ca: enhancement in combination with doxorubicin
SOX9↓, SOX9↓
ER Stress↑, Cervix Ca : ER-stress protein GRP78↑, CHOP↑, calpain↑
GRP78/BiP↑,
cal2↓,
AMPK↓, Breast Ca: AMPK/mTOR signaling↓
mTOR↓,
ROS↓, Boswellia extracts and its phytochemicals reduced oxidative stress (in terms of inhibition of ROS and RNS generation)
Bax:Bcl2↑, marked increase in the BAX/BCL-XL ratio
PPARα↓, carvacrol reduced PPARα expression and NF-κB nuclear localization, increased SIRT1 and SIRT3 levels, selectively suppressed MMP-3
NF-kB↓,
SIRT1↑,
SIRT3↑,
MMP3↓,
selectivity↑, Carvacrol selectively targets breast cancer-associated fibroblasts by inducing mitochondria-related apoptotic signaling while largely sparing normal fibroblasts.
Bcl-2↓, In breast cancer lines, CV has been reported to down-regulate Bcl-2, up-regulate Bax, and induce caspase-3/-6/-9 activation in a dose-dependent manner, consistent with mitochondrial apoptosis
BAX↑,
Casp3↑,
Casp6↑,
Casp9↑,
mt-Apoptosis↑,
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in-vitro, |
Colon, |
HCT116 |
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TumCP↓, CuC can effectively inhibit the proliferation and migration of HCT-116
TumCMig↓, CuC inhibits the migration of HCT-116 colon cancer cells and downregulates migration-associated genes
TumCG↓, CuC also can suppress the colon tumor growth in vivo, while reducing the expression of placental growth factor, MMP-1, MMP-3, MMP-9, and MMP-13 both in vitro and in vivo, consistent with the predicted results.
MMP1↓,
MMP3↓,
MMP9↓,
MMP13↓,
Apoptosis↑, CuC inhibits proliferation and promotes apoptosis in HCT-116 colon cancer cells
*COX2/PTGS2↓, Curcumin downregulates the cyclooxygenase-2 (COX-2) pathway, reducing the production of prostaglandins associated with inflammation
*Inflam↓,
*5LO↓, directly inhibits lipoxygenase (LOX)
*NO↓,
*NF-kB↓,
*TNF-α↓,
*IL1↓,
*IL2↑,
*IL6↓,
*IL8↓,
*IL12↓,
*MCP1/CCL2↓,
*PGE2↓,
*MMP2↓,
*MMP3↓,
*MMP9↓,
*NLRP3↓,
*ROS↓, arthritis(basically normal cell)
*ALAT↓, emodin can improve ethanol-mediated hepatic steatosis and treat alcoholic liver disease by downregulating the levels of alanine aminotransferase (ALT), triglyceride, and aspartate aminotransferase
*AST↓,
*ROS↓, emodin exerts potential antioxidant effects, such as regulating the free radical and reactive oxygen species (ROS) levels and affecting oxidative stress-induced damage
*cardioP↑, In cardiovascular diseases, emodin exerts potential therapeutic effects on diabetic retinopathy by inhibiting aldose reductase activity and improving retinal angiogenesis
*TNF-α↓, Emodin can also significantly inhibit the expression of TNF-α and activate the NF-κB signaling pathway in the local myocardial infarction area and can play a protective role in myocardial ischemia
*NF-kB↓,
*Inflam↓, Emodin Affects RA Procession by Regulating Inflammatory Cytokines
*AntiArt↑,
*PGE2↓, PGE2, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 decreased expression
*MMP3↓,
*MMP13↓,
*COX2/PTGS2↓, Emodin also reduces the plasma levels of TNF-α and IL-6, PGE(2) production, and cyclooxygenase 2 (COX-2) protein expression in synovial tissue [102].
*AntiCan↑, Emodin is a natural anthraquinone compound with various pharmacological effects, including anticancer, anti-inflammatory, antiviral, antibacterial, antiallergic, antiosteoporosis, antidiabetic, immunosuppressive, neuroprotective, and hepatoprotective
*neuroP↑,
*hepatoP↑,
OS↑, Emodin increased the survival percentage and reduced the number of hepatic nodules compared to the HCC group. Therefore, emodin extended the survival percentage of the HCC group by about 45%
PKCδ↓, emodin reduced the elevated expression of both mRNA and proteins of all PKC, ERK5, ADAMTS4, MMP3, and VEGF compared with the HCC group
ERK5↓,
MMP3↓,
VEGF↓,
NRF2↑, emodin increased the expression of mRNA and proteins of Nrf2, HO-1, and aggrecan compared with the HCC group.
HO-1↑,
MDA↓, HCC rats exhibited a 4.71-fold increase in hepatic levels of MDA and a 61% reduction in the hepatic concentration of reduced glutathione compared to the control rats. Treatment with emodin reversed these effects
AFP↓, emodin succeeded in significantly decreasing the upregulated serum AFP (about 71% reduction), restoring it to its normal level in the control group
PI3K↓, block multiple signaling pathways such as the phosphatidylinositol-3-kinase/protein kinase
B/mammalian target of rapamycin (PI3K/Akt/mTOR) and p38
Akt↓,
mTOR↓,
p38↓,
*antiOx↑, antioxidant, anti-inflammatory, antiangiogenic, hypolipidemic, neuroprotective, and antitumor effect
*neuroP↑,
Casp3↑, U266 cancer cell line through activation of caspase-3, downregulation of Bcl-2 and Mcl-1L, upregulation of Bax, Bim and Bad
Bcl-2↓,
Mcl-1↓,
BAX↑,
BIM↑,
BAD↑,
AMPK↑, activation of 5'adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and decreased phosphorylation of AKT and mTOR were also observed
ACC↑,
DNAdam↑, DNA fragmentation, mitochondrial membrane depolarizatio
MMP↓,
eff↑, fisetin in combination with a citrus flavanone, hesperetin mediated apoptosis by
mitochondrial membrane depolarization and caspase-3 act
ROS↑, NCI-H460 human non-small cell lung cancer line, fisetin generated reactive oxygen species (ROS), endoplasmic reticulum (ER) stress
cl‑PARP↑, fisetin treatment resulted in PARP cleavage
Cyt‑c↑, release of cyt. c
Diablo↑, release of cyt. c and Smac/DIABLO from mitochondria,
P53↑, increased p53 protein levels
p65↓, reduced phospho-p65 and Myc oncogene expression
Myc↓,
HSP70/HSPA5↓, fisetin causes inhibition of proliferation by the modulation of heat shock protein 70 (HSP70), HSP27
HSP27↓,
COX2/PTGS2↓, anti-proliferative effects of fisetin through the activation of apoptosis via inhibition of cyclooxygenase-2 (COX-2) and Wnt/EGFR/NF-κB signaling pathways
Wnt↓,
EGFR↓,
NF-kB↓,
TumCCA↑, The anti-proliferative effects of fisetin and hesperetin were shown to be occurred through S, G2/M, and G0/G1 phase arrest in K562 cell progression
CDK2↓, decrease in levels of cyclin D1, cyclin A, Cdk-4 and Cdk-2
CDK4↓,
cycD1/CCND1↓,
cycA1/CCNA1↓,
P21↑, increase in p21
CIP1/WAF1
levels in HT-29 human colon cancer cell
MMP2↓, fisetin has exhibited tumor inhibitory effects by blocking matrix metalloproteinase-2 (MMP- 2) and MMP-9 at mRNA and protein levels,
MMP9↓,
TumMeta↓, Antimetastasis
MMP1↓, fisetin also inhibited the MMP-14,
MMP-1, MMP-3, MMP-7, and MMP-9
MMP3↓,
MMP7↓,
MET↓, promotion of mesenchymal to epithelial transition associated with a decrease in mesenchymal markers i.e. N-cadherin, vimentin, snail and fibronectin and an increase in epithelial markers i.e. E-cadherin
N-cadherin↓,
Vim↓,
Snail↓,
Fibronectin↓,
E-cadherin↑,
uPA↓, fisetin suppressed the expression and activity of urokinase plasminogen activator (uPA)
ChemoSen↑, combination treatment of fisetin and sorafenib reduced the migration and invasion of BRAF-mutated melanoma cells both in in-vitro
EMT↓, inhibited epithelial to mesenchymal transition (EMT) as observed by a decrease in N-cadherin, vimentin and fibronectin and an increase in E-cadherin
Twist↓, inhibited expression of Snail1, Twist1, Slug, ZEB1 and MMP-2 and MMP-9
Zeb1↓,
cFos↓, significant decrease in NF-κB, c-Fos, and c-Jun levels
cJun↓,
EGF↓, Fisetin inhibited epidermal growth factor (EGF)
angioG↓, Antiangiogenesis
VEGF↓, decreased expression of endothelial nitric oxide synthase
(eNOS) and VEGF, EGFR, COX-2
eNOS↓,
*NRF2↑, significantly increased nuclear translocation of Nrf2 and antioxidant response element (ARE) luciferase activity, leading to upregulation of HO-1 expression
HO-1↑,
NRF2↓, Fisetin also triggered the suppression of Nrf2
GSTs↓, declined placental type glutathione S-transferase (GST-p) level in the liver of the fisetin- treated rats with hepatocellular carcinoma (HCC)
ATF4↓, Fisetin also rapidly increased the levels of both Nrf2 and ATF4
NRF2↑, fisetin increased the protein level and accumulation Nrf2 and down regulated the protein levels of Keap1
Keap1↓,
ChemoSen↑, In vitro studies showed that fisetin and quercetin could also act against chemotherapeutic resistance in several cancers
BioAv↓, Fisetin has low aqueous solubility and bioavailability
Cyt‑c↑, release of cytochrome c from mitochondria, caspase-3 and caspase-9 mRNA and protein expression, and B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) levels, were found to be regulated in the fisetin-treated cancer cell line
Casp3↑,
Casp9↑,
BAX↑,
tumCV↓, fisetin at 5–80 µM significantly reduced the viability of A431 human epidermoid carcinoma cells by the release of cytochrome c,
Mcl-1↓, reducing the anti-apoptotic protein expression of Bcl-2, Bcl-xL, and Mcl-1 along with elevation of pro-apoptotic protein expression (Bax, Bak, and Bad) and caspase cleavage and poly-ADP-ribose polymerase (PARP) protein
cl‑PARP↑,
IGF-1↓, fisetin promoted caspase-8 and cytochrome c expression, possibly by impeding the aberrant activation of insulin growth factor receptor 1 and Akt
Akt↓,
CDK6↓, fisetin binds with CDK6, which in turn blocks its activity with an inhibitory concentration (IC50) at a concentration of 0.85 μM
TumCCA↑, fisetin is identified as a regulator of cell cycle checkpoints, leading to cell arrest through CDK inhibition in HL60 cells and astrocyte cells over the G0/G1, S, and G2/M phases
P53?, exhibiting elevated levels of p53
cycD1/CCND1↓, 10–60 μM fisetin concentration, prostate cancer cells PC3, LNCaP, and CWR22Ry1 had decreased cellular viability and decreased levels of D1, D2, and E cyclins and their activating partners CDK2, and CDKs 4/ 6,
cycE/CCNE↓,
CDK2↓, decreased levels of D1, D2, and E cyclins and their activating partners CDK2, and CDKs 4/ 6,
CDK4↓,
CDK6↓,
MMP2↓, fisetin displayed tumor inhibitory effects by blocking MMP-2 and MMP-9 at mRNA and protein levels in prostate PC-3 cells
MMP9↓,
MMP1↓, Similarly, fisetin can also inhibit MMP-1, MMP-9, MMP-7, MMP-3, and MMP-14 gene expression linked with ECM remodeling in human umbilical vascular endothelial cells (HUVECs) and HT-1080 fibrosarcoma cells [9
MMP7↓,
MMP3↓,
VEGF↓, fisetin in a concentration-dependent manner (10–50 μM concentration) significantly inhibited regular serum, growth-enhancing supplement, and vascular endothelial growth factor (VEGF)
PI3K↓, fisetin inhibited PI3K expression and phosphorylation of Akt
mTOR↓, fisetin treatment activated the apoptotic process through inhibiting both PI3K and mammalian target of rapamycin (mTOR) signaling pathways
COX2/PTGS2↓, fisetin resulted in activation of apoptosis and inhibition of COX-2 and the Wnt/EGFR/NF-kB pathway
Wnt↓,
EGFR↓,
NF-kB↓,
ERK↓, Fisetin is one of the flavonoids that has been found to suppress ERK1/2 signaling in human gastric (SGC7901), hepatic (HepG2), colorectal (Caco-2)
ROS↑, fisetin induced ROS generation and suppressed ERK through its phosphorylation
angioG↓, fisetin-induced anti-angiogenesis led to reduced VEGF and epidermal growth factor receptor (EGFR) expression
TNF-α↓, Fisetin suppressed IL-1β-mediated expression of inducible nitric oxide synthase, nitric oxide, interleukin-6, tumor necrotic factor-α, prostaglandin E2, cyclooxygenase-2 (iNOS, NO, IL-6, TNF-α, PGE2, and COX-2),
PGE2↓,
iNOS↓,
NO↓,
IL6↓,
HSP70/HSPA5↝, fisetin-mediated inhibition of cellular proliferation by HSP70 and HSP27 regulation
HSP27↝,
AntiCan↑, garcinol has demonstrated huge potential as an anti-cancer agent, inhibiting tumor growth, progression, and metastasis in various cancers, such as lung, liver, pancreas, prostate, breast, colon, and brain cancers.
TumCG↓,
TumMeta↓,
toxicity↓, garcinol offers a safer alternative with broad-spectrum activity and minimal adverse effects.
Apoptosis↑, anti-tumorigenic properties are linked to apoptosis induction, angiogenesis inhibition, and modulation of the tumor microenvironment
angioG↓,
*BioAv↝, nano-delivery systems have improved its bioavailability and therapeutic efficacy, overcoming challenges related to its solubility and stability.
HATs↓, Garcinol primarily targets histone acetyltransferases (HATs), particularly p300 and CBP (CREB-binding protein), leading to structural modifications in these proteins.
p300↓,
CBP↓,
PI3K↓, Garcinol exerts its anticancer effects primarily by modulating key signaling pathways, including the PI3K/AKT, NF-κB, JAK/STAT, and MAPK pathways.
Akt↓,
NF-kB↓,
STAT↓,
mTOR↓, figure 1
DFF45↓,
survivin↓,
N-cadherin↓,
Twist↓,
MMP2↓,
MMP3↓,
MMP9↓,
Mcl-1↓,
EZH2↓,
NOTCH↓,
CXCR4↓,
PGE2↓,
VEGF↓,
mPGES-1↓,
CycB/CCNB1↓,
CDK2↓,
CDK4/6↓,
iNOS↓,
COX2/PTGS2↓,
IL1↓,
TNF-α↓,
PARP↑,
Bcl-2↓,
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in-vitro, |
Colon, |
Caco-2 |
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AntiCan↑, Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon.
TumCA↓, IP6 has been demonstrated to inhibit cancer cell adhesion and migration.
TumCMig↓,
MMP13↓, A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6.
MMP3↓,
MMP2↓,
TIMP1↓,
MMP1↓, IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture.
MMP9↓,
TIMP2↓,
*antiOx↓, Kaempferol is a natural flavonoid with antioxidant, anti-inflammatory, neuroprotective, and anticancer effects.
*Inflam↓,
*neuroP↓,
*AntiCan↑,
DNAdam↓, kaempferol inhibited Nrf2 and induced ROS accumulation after 48 h of treatment, thereby making the NSCLC cells sensitive to apoptosis
Casp3↑,
Casp9↑,
p‑AMT/GCST/T-protein↑,
ROS↑, with ROS generation
NRF2↑, Kaempferol has been reported to activate Nrf2 and its downstream signaling pathways in multiple human cancer cell models, including MCF-7 breast cancer cells
Apoptosis↑, inducing apoptosis by increasing cleaved PARP and Bax and downregulating Bcl-2 expression, inducing cell cycle arrest at the G2/M phase;
cl‑PARP↓,
BAX↑,
Bcl-2↓,
TumCCA↓,
angioG↓, inhibiting the angiogenic and metastatic potential of tumors by downregulating MMP-3 and MMP-9 levels
MMP3↓,
MMP9↓,
ChemoSen↑, Kaempferol holds promise for boosting the efficacy of anticancer agents, complementing their effects, or reversing developed chemoresistance.
BioAv↓, Kaempferol has poor water solubility and has been studied extensively for its pharmacokinetic properties both in vitro and in vivo.
Glycolysis↓, They also demonstrated decreased aerobic glycolysis,
cl‑PARP↑, Their cell growth inhibition and apoptosis were linked to the activation of PARP cleavage
Ca+2↑, induction of apoptosis with a significant increase in cytoplasmic Ca2+ and decrease in mitochondria membrane potential (Δψm) levels in US-2 OS cells
MMP↓,
ER Stress↑, induction of various endoplasmic reticulum stress-related proteins and apoptotic proteins, including GRP78, GRP94, GADD153, ATF-6α, ATF-6β, caspase-4, caspase-12, calpain 1, caspase 3, and caspase 6 activity
GRP78/BiP↑,
CHOP/DDIT3↑,
ATF6↑,
angioG↓, Kaempferol could also induce anti-angiogenic potential, which is another major clinical challenge faced in cancer therapy.
VEGF↓, The marked decrease in the mRNA and protein levels of Vascular Endothelial Growth Factor (VEGF)
Hif1a↓, kaempferol, was also able to downregulate the expression of HIF-α (a regulator of VEGF)
chemoP↑, Interestingly, kaempferol also helps alleviate the serious adverse effects of standard chemotherapeutic agents.
*ROS↓, kaempferol reversed the vascular doxorubicin-induced vascular toxicity by reducing oxidative stress, i
NRF2↑, Kaempferol has been reported to activate Nrf2 and its downstream signaling pathways in multiple human cancer cell models, including MCF-7 breast cancer cells
BioAv↑, kaempferol gold nanoparticles (KAuNPs) using the reactive -OH group in the catechol ring of kaempferol and showed excellent biocompatibility with biological systems. They further observed a significant increase in the cytotoxic potential of KAuNP
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.
| - |
in-vitro, |
Lung, |
A549 |
|
|
|
- |
in-vitro, |
Lung, |
H460 |
|
|
|
TumCMig↓, LicA exhibited effective inhibition of cell migration and invasion of A549 and H460 cells under non-cytotoxic concentrations.
TumCI↓,
MMP1↓, LicA was also found to significantly inhibit the proteins and messenger RNA (mRNA) expression of MMP-1 and MMP-3 in A549 cells.
MMP3↓,
p‑Akt↓, LicA-inhibited activation of the phosphorylation of Akt
Akt↓, LicA inhibits Akt signaling pathways and downstream transcription factors Sp1 expression.
Sp1/3/4↓,
Bcl-2↓, Multiple licorice constituents have been shown to bind to and inhibit the activities of various cellular targets, including B-cell lymphoma 2, cyclin-dependent kinase 2, phosphatidylinositol 3-kinase, c-Jun N-terminal kinases, mammalian target of rap
CDK2↓,
PI3K↓,
cJun↓,
mTOR↓,
NF-kB↓, nuclear factor-κB, signal transducer and activator of transcription 3, vascular endothelial growth factor, and matrix metalloproteinase-3, resulting in reduced carcinogenesis in several in vitro and in vivo models with no evident toxicity
VEGF↓,
MMP3↓,
toxicity↓,
Dose↑, European Union established a temporary upper limit of 100 mg/day for glycyrrhizin consumption (about the amount found in 60–70 g licorice).
chemoP↑, Licorice has long been used as an antidote to counteract the toxicity of chemotherapeutic treatment
*antiOx↑, including antioxidant and anti-inflammatory properties, as well as a protective effect on several organs
*Inflam↓,
Dose↝, The main sweet-tasting ingredient of G. glabra (licorice) root is glycyrrhizin (or glycyrrhizinic acid or GA).
*COX2/PTGS2↓, glycyrrhizin and 18β-glycyrrhetinic acid have been defined by different investigators as significant inhibitors of inflammatory factors, such as cyclooxygenase-2 (COX-2), HMGP 1, inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), IL-10, t
*iNOS↓,
*IL6↓,
*IL10↓,
*PGE2↓, licochalcone A and licochalcone B inhibit IL-6 and PGE2 in LPS-induced macrophage cells,
*IκB?, isoliquiritigenin and isoliquiritin inhibit inhibitory κBα (IκBα) phosphorylation and degradation, and increase the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 in LPS-induced macrophage cells
*NRF2↑,
*HO-1↑,
*lipid-P↓, figure 2
*ROS↓,
*Catalase↑,
*GPx↑,
*SOD↑,
Apoptosis↑, The glycyrrhetinic acid and its derivatives induce mitochondrial-mediated apoptosis in cancer cells, as it was found in a study conducted by Lin et al119 where apoptosis was induced by the generation of reactive oxygen species (ROS)
ROS↑,
TumCP↓, GA, another flavonoid extracted from the roots of licorice also induces apoptosis and suppresses the proliferation of MDA-MB-231 breast cancer cells by increased generation of ROS.123
TumCCA↑, GA induces cell cycle arrest at G1/S phase in gastric cancer cells by downregulating the cyclin E1, cyclin E2, and cyclin D1-3 levels causing cell death in these cancer cells.
cycE/CCNE↓,
cycD1/CCND1↓,
p‑GSK‐3β↓, SK-MEL-28 and SK-MEL-5 Induced apoptosis ↓G1 phase, ↓cyclin D1, ↓cyclin E, ↓p-Akt, ↓p-GSK3β, ↓p-JNK1/2, ↓PI3K, ↓MKK4, ↓MKK7
PI3K↓,
MKK4↓,
MKK7↓,
HSP90↓, HT-29 Induced apoptosis ↓Proliferation, ↓viability of cells, ↑cell death of cancer cells, ↓HSP90
LC3‑Ⅱ/LC3‑Ⅰ↑, MKN28 Inhibited metastasis ↓Proliferation and metastasis, ↓migration and invasion, ↑LC3II/LC3I ratio, ↑Beclin 1, ↓p62, ↓p-Akt, ↓p- mTOR
Beclin-1/ATG6↑,
p62↓,
p‑Akt↓,
cl‑Casp9↑, Caki Induced apoptosis ↑Cleavage of caspase-9, caspase-7 and caspase-3, and PARP, ↑Bax, ↓Bcl-2, ↓ Bcl-xL, ↑cyt. c release, ↑p53, ↓MDM2, ↑ROS levels, ↓STAT3, ↓cyclin D1 and D2, ↓p-JAK2,
cl‑Casp7↑,
cl‑Casp3↑,
cl‑PARP↑,
BAX↑,
Cyt‑c↑,
P53↑,
STAT3↓,
E-cadherin↑, ↑E-cadherin ↓Vimentin, ↓N-cadherin,
Vim↓,
N-cadherin↓,
CD31/PECAM-1↓, ↓VEGF-A, ↓CD31 ↓HIF-1α, ↓iNOS, ↓COX-2
Hif1a↓,
iNOS↓,
DNAdam↑, ↑Nuclear condensation, ↑ nuclear fragmentation, ↑ apoptotic ratio, ↑decrease in the ΔΨ m, ↑Bax, ↑ Bim, ↑Apaf-1, ↑caspase-9, ↑caspase-3, ↓Bcl-2, ↑CDK2
MMP↓,
BIM↑,
APAF1↑,
PCNA↓, ↓PCNA, ↓MMP2, ↓ MMP9, ↑caspase-3, ↓p-PI3K, ↓p-Akt
toxicity↝, In addition, based on a case report, excessive consumption of licorice may also lead to toxic consequences in the form of thrombocytopenia.
eff↑, A clinical stage II preliminary trial revealed that licorice root extract in combination with docetaxel works in treating patients with hormonal therapy resistant metastatic prostate tumors
AntiAg↑, PL has been shown to exert in vitro antiplatelet aggregation effect induced by agonists
such as collagen, adenosine 50-diphosphate (ADP), arachidonic acid (AA) and thrombin.
neuroP↑, Neuroprotective activity of PL and its derivatives
Inflam↓, Anti-inflammatory activity of PL and its derivatives
NO↓, production of NO and PGE2 was significantly inhibited after the treatment of PL.
PGE2↓,
MMP3↓, PL also significantly suppressed the production of MMP-3 and MMP-13
MMP13↓,
TumCMig↓, PL inhibited the proliferation, induced the apoptosis and reduced the migration and invasion of RA FLS by activating the p38, JNK, NF-kB and STAT3 pathways
TumCI↓,
p38↑,
JNK↑,
NF-kB↑,
ROS↑, PL has been reported to selectively induce apoptotic by ROS accumulation in cancer cells via different
molecular mechanisms.
FOXM1↓, PL inhibited proteasome including suppression of FOXM1
TrxR1↓, induction of ROS by directly inhibiting thioredoxin reductase 1 (TrxR1) activity
GSH↓, Wang et al. demonstrated that PL could inhibit both glutathione and thioredoxin and thus induce ROS
elevation,
Trx↓,
cMyc↓, downregulation of c-Myc and LMP1 and the Caspase-3-dependent apoptosis of Burkitt lymphoma cells in vitro.
Casp3↑,
Bcl-2↓, PL could downregulate Bcl-2 and Mcl-1 and decrease the expression of STAT-3
Mcl-1↓,
STAT3↓, Bharadwaj et al. identiï¬ed PL as a direct STAT3 inhibitor
AR↓, Golovine et al. demonstrated for the ï¬rst time that PL rapidly reduced the androgen receptor protein level of prostate cancer cells
DNAdam↑, inducing DNA damage,
| - |
in-vitro, |
BC, |
MCF7 |
|
|
|
- |
in-vitro, |
BC, |
MDA-MB-231 |
|
|
|
- |
in-vivo, |
NA, |
NA |
|
|
|
MMP2↓, quercetin treatment down-regulated the expression of cell migration marker proteins, such as matrix metalloproteinase 2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF).
MMP9↓, level of MMP-2,
MMP-9 and VEGF was all strongly cut down by quercetin treatment compared with control group
VEGF↓,
Glycolysis↓, quercetin successfully blocked cell glycolysis by inhibiting the level of glucose uptake and the production of lactic acid
lactateProd↓,
PKM2↓, and also decreased the level of glycolysis-related proteins Pyruvate kinase M2 (PKM2), Glucose transporter1(GLUT1) and Lactate dehydrogenase A (LDHA).
GLUT1↓,
LDHA↓,
TumAuto↑, quercetin induced obvious autophagy via inactivating the Akt-mTOR pathway
Akt↓,
mTOR↓,
TumMeta↓, Quercetin suppressed the progression of breast cancer by inhibiting tumor metastasis and glycolysis in vivo
MMP3↓, quercetin effectively suppressed the invasion and migration ability of breast cancer cells through
suppressing the expression of MMP-3, MMP-9 and VEGF,
eff↓, down-regulating the expression of PKM2, which regulated the final step of glycolysis, could effectively enhance the chemotherapeutic effect of THP
GlucoseCon↓, we found that quercetin effectively suppressed the level of glucose uptake and the production of lactic acid, and also down-regulated the expression of glycolysis-related proteins PKM2, LDHA and GLUT1,
lactateProd↓,
TumAuto↑, quercetin treatment induced obvious autophagy in MCF-7 and
MDA-MB-231 cells via inactivating the Akt-mTOR pathway
LC3B-II↑, showing obvious conversion of
LC3B-I to LC3B-II
AntiTum↑, anti-tumor capabilities of resveratrol and then emphasizes the significant role of the PI3K/Akt signaling pathway in the progression of multiple malignancies
PI3K↓,
Akt↓,
*AntiAge↑, Multiple studies in various organisms have consistently indicated that resveratrol can extend a healthy lifespan through sirtuin 1 (SIRT1) pathway activation
*SIRT1↑,
*lipid-P↓, it safeguards cell membranes from lipid peroxidation and protects DNA from damage caused by reactive oxygen species (ROS)
*ROS↓,
*BioAv↓, low bioavailability is another major challenge in clinical translation of resveratrol.
*NRF2↑, Resveratrol exerts potent antioxidant effects by activating the Nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme oxygenase-1 (HO-1) signaling pathway.
*HO-1↑,
SOD↑, In various cancer types, including prostate, liver, and breast cancer, even low concentrations of resveratrol treatment significantly enhance superoxide dismutase (SOD)
HDAC1↓, Resveratrol also inhibits the MTA1/HDAC1 complex, leading PTEN reactivation and subsequently suppressing the Akt pathway.
PTEN↑,
P53↑, Resveratrol activates p53
TumCCA↑, A study found that resveratrol arrested the cell cycle at G0/G1, suppressed cell proliferation, and stimulated apoptosis in a concentration- and time-dependent manner
TumCI↓, resveratrol effectively inhibits tumor invasion and metastasis by inhibiting signaling pathways associated with EMT
TumMeta↓,
EMT↓,
MMPs↓, Resveratrol has been proposed to have a potential role in suppressing the expression of matrix metalloproteinases (MMPs), particularly MMP-9,
MMP9↓,
angioG↓, and angiogenesis-related markers such as vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), or fibroblast growth factor (FGF)-2
VEGF↓,
EGFR↓,
FGF21↓,
HIF-1↓, resveratrol significantly hinders the proliferation of human ovarian cancer and angiogenesis by diminishing the generation of HIF-1 and VEGF.
*neuroP↑, resveratrol can use as a therapeutic option in cardiovascular health, metabolic diseases, neuroprotection, and malignancies
*cardioP↑, it acts as a cardiovascular protector in the heart
BMPs↑, Resveratrol exerts its anti-cancer effects by suppressing the PI3K/Akt pathway through the upregulation of BMP7
ROS↑, Lung Cancer: These effects were attributed to alterations in mitochondrial metabolism and the generation of excessive reactive oxygen species (ROS)
Vim↓, The researchers discovered that resveratrol lowered the amounts of vimentin, N-cadherin, MMP-3, and MMP-13 proteins while raising the levels of E-cadherin protein in HeLa and SiHa cells
N-cadherin↓,
MMP3↓,
MMP13↓,
E-cadherin↑,
Ki-67↓, A phase I trial on CRC demonstrated that resveratrol reduced cell proliferation markers, such as Ki-67, while increasing apoptotic activity in tumor tissues
| - |
Review, |
Nor, |
NA |
|
|
|
- |
NA, |
AD, |
NA |
|
|
|
*antiOx↑, In preclinical models of cognitive decline, resveratrol displays potent antioxidant activity by scavenging free radicals, reducing quinone reductase 2 activity and upregulating endogenous enzymes.
*ROS↓,
*cognitive↑,
*neuroP↑,
*SIRT1↑, By inducing SIRT1, resveratrol may promote neurite outgrowth and enhance neural plasticity in the hippocampal region
*AMPK↑, Resveratrol also induces neurogenesis and mitochondrial biogenesis by enhancing AMP-activated protein kinase (AMPK), which is known to stimulate neuronal differentiation and mitochondrial biogenesis in neurons.
*GPx↑, figure 1
*HO-1↑,
*GSK‐3β↑,
*COX2/PTGS2↓,
*PGE2↓, Resveratrol also inhibits pro-inflammatory enzyme (i.e., COX-1 and -2) expression, reduces NF-κB activation as well as PGE2, NO, and TNF-α production, and cytokine release
*NF-kB↓,
*NO↓,
*Casp3↓,
*MMP3↓,
*MMP9↓,
*MMP↑, resveratrol attenuated ROS production and mitochondrial membrane-potential disruption; moreover, it restored the normal levels of glutathione (GSH) depleted by Aβ1-42
*GSH↑,
*other↑, resveratrol significantly increased cerebral blood flow (CBF) in the frontal cortex of young healthy humans.
*BioAv↑, receiving 200 mg/day of resveratrol in a formulation with quercetin 320 mg [53], in order to increase its bioavailability,
*memory↑, Resveratrol supplementation induced retention of memory and improved the functional connectivity between the hippocampus and frontal, parietal, and occipital areas, compared with placebo
*GlutMet↑, Also, glucose metabolism was improved and this may account for some of the beneficial effects of resveratrol on neuronal function.
*BioAv↓, The main problems related to the therapeutic or preventive use of resveratrol are linked to its low oral bioavailability and its short half-life in serum
*Half-Life↓,
*toxicity∅, On the other hand, the tolerability and safety profile of resveratrol is very high
| - |
in-vitro, |
NPC, |
HONE1 |
|
|
|
- |
in-vitro, |
NPC, |
SUNE-1 |
|
|
|
TumCP↓, Shikonin treatment effectively suppressed cell proliferation and induced obvious cell apoptosis compared with the control.
Apoptosis↑,
TumCMig↓, Shikonin treatment suppressed cell migration and invasion effectively.
TumCI↓,
GlucoseCon↓, Shikonin treatment suppressed cell glucose uptake, lactate release and ATP level.
lactateProd↓,
ATP↓,
PKM2↓, activity of PKM2 was also largely inhibited by Shikonin
PI3K↓, PI3K/AKT signal pathway was inactivated by Shikonin treatment
Akt↓,
MMP3↓, MMP-3 and MMP-9 was decreased and the expression of TIMP was increased by Shikonin in HONE1 and SUNE-1 cells
MMP9↓,
TIMP1↑,
Showing Research Papers: 1 to 22 of 22
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 22
Pathway results for Effect on Cancer / Diseased Cells:
NA, unassigned(tgid=0) ⓘ
p‑AMT/GCST/T-protein↑, 1, ATG13↑, 1, ATG16L1↑, 1, RUBCN↓, 1, THEM4/CTMP↑, 1, TNFRSF25/DR3/APO3/LARD/TRAMP/WSL1↑, 1, ULK1/ATG1↑, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
GSH↓, 1, GSTs↓, 1, HO-1↑, 2, Keap1↓, 1, MDA↓, 1, NRF2↓, 1, NRF2↑, 4, ROS↓, 1, ROS↑, 9, SIRT3↑, 1, SOD↑, 1, Trx↓, 1, TrxR1↓, 2,
Mitochondria & Bioenergetics(tgid=3) ⓘ
AIF↑, 1, ATP↓, 2, CDC2↓, 1, CDC25↓, 4, EGF↓, 1, MKK4↓, 1, MKK7↓, 1, MMP↓, 5, mtDam↑, 1, XIAP↓, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
ACC↑, 1, AMPK↓, 1, AMPK↑, 2, ATG7↑, 1, cMyc↓, 1, FGF21↓, 1, GlucoseCon↓, 2, Glycolysis↓, 3, HK2↓, 1, lactateProd↓, 3, LDHA↓, 1, PDK1 / PDPK1↓, 1, PKM2↓, 2, PPARα↓, 1, SIRT1↑, 1,
Cell Death(tgid=5) ⓘ
Akt↓, 9, p‑Akt↓, 3, APAF1↑, 2, Apoptosis↑, 6, mt-Apoptosis↑, 2, BAD↑, 2, BAX↑, 7, Bax:Bcl2↑, 2, Bcl-2↓, 8, Bcl-xL↓, 2, BIM↑, 2, Casp↑, 1, Casp3↓, 1, Casp3↑, 7, cl‑Casp3↑, 1, Casp6↑, 1, cl‑Casp7↑, 1, Casp8↑, 2, Casp9↑, 4, cl‑Casp9↑, 1, CBP↓, 1, Cyt‑c↑, 6, Diablo↑, 2, DR5↑, 2, Fas↑, 2, FasL↑, 1, IAP1↓, 1, ICAD↓, 1, iNOS↓, 3, JNK↑, 1, MAPK↓, 1, Mcl-1↓, 4, MDM2↓, 2, Myc↓, 1, p38↓, 1, p38↑, 1, survivin↓, 4,
Kinase & Signal Transduction(tgid=6) ⓘ
SOX9↓, 1, Sp1/3/4↓, 2, TSC2↑, 1,
Transcription & Epigenetics(tgid=7) ⓘ
cJun↓, 2, EZH2↓, 1, HATs↓, 1, other↓, 1, tumCV↓, 1,
Protein Folding & ER Stress(tgid=8) ⓘ
ATF6↑, 1, CHOP/DDIT3↑, 3, eIF2α↓, 1, ER Stress↑, 3, GRP78/BiP↑, 2, HSP27↓, 1, HSP27↝, 1, HSP70/HSPA5↓, 1, HSP70/HSPA5↝, 1, HSP90↓, 1, PERK↑, 1, UPR↑, 1,
Autophagy & Lysosomes(tgid=9) ⓘ
ATG3↑, 1, ATG5↑, 1, Beclin-1/ATG6↑, 2, LC3‑Ⅱ/LC3‑Ⅰ↑, 2, LC3B-II↑, 1, LC3II↑, 1, p62↓, 1, p62↑, 1, TumAuto↑, 4,
DNA Damage & Repair(tgid=10) ⓘ
ATM↑, 1, DFF45↓, 1, DNAdam↓, 1, DNAdam↑, 4, P53?, 1, P53↑, 4, PARP↑, 1, cl‑PARP↓, 1, cl‑PARP↑, 6, PCNA↓, 1,
Cell Cycle & Senescence(tgid=11) ⓘ
p‑CDK1↓, 1, CDK2↓, 4, CDK4↓, 2, cycA1/CCNA1↓, 1, CycB/CCNB1↓, 3, cycD1/CCND1↓, 4, cycE/CCNE↓, 2, P21↑, 2, RB1↑, 1, p‑RB1↓, 1, TumCCA↓, 1, TumCCA↑, 6,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
4E-BP1↓, 1, cFos↓, 1, p‑cMET↑, 1, CSCs↓, 1, EMT↓, 3, EMT↑, 1, ERK↓, 3, p‑ERK↓, 1, ERK5↓, 1, FOXM1↓, 2, GSK‐3β↓, 1, p‑GSK‐3β↓, 1, HDAC1↓, 1, IGF-1↓, 1, mTOR↓, 8, NOTCH↓, 1, p300↓, 1, P70S6K↓, 1, PI3K↓, 8, PTEN↑, 1, RAS↓, 1, STAT↓, 1, STAT3↓, 3, TOP2↓, 1, TumCG↓, 2, Wnt↓, 3,
Migration(tgid=13) ⓘ
AntiAg↑, 1, Ca+2↑, 2, cal2↓, 1, CD31/PECAM-1↓, 1, CDK4/6↓, 1, COL1A1↓, 1, E-cadherin↑, 4, FAK↓, 1, Fibronectin↓, 1, ITGA5↑, 1, ITGB1↑, 1, Ki-67↓, 1, LAMA5↑, 1, MET↓, 1, MMP-10↓, 1, MMP1↓, 6, MMP13↓, 5, MMP2↓, 6, MMP3↓, 17, MMP7↓, 2, MMP9↓, 11, MMPs↓, 1, N-cadherin↓, 4, PKCδ↓, 2, Rho↓, 1, ROCK1↓, 1, Snail↓, 1, Snail↑, 1, TGF-β↓, 1, TIMP1↓, 1, TIMP1↑, 1, TIMP2↓, 1, TSC1↑, 1, TumCA↓, 1, TumCI↓, 6, TumCMig↓, 6, TumCP↓, 5, TumMeta↓, 5, Twist↓, 2, uPA↓, 2, Vim↓, 4, Zeb1↓, 1, Zeb1↑, 1, β-catenin/ZEB1↓, 1,
Angiogenesis & Vasculature(tgid=14) ⓘ
angioG↓, 9, ATF4↓, 1, ATF4↑, 1, EGFR↓, 4, eNOS↓, 1, HIF-1↓, 1, Hif1a↓, 3, NO↓, 2, VEGF↓, 10,
Barriers & Transport(tgid=15) ⓘ
GLUT1↓, 2,
Immune & Inflammatory Signaling(tgid=16) ⓘ
CD4+↓, 1, COX2/PTGS2↓, 5, CXCR4↓, 1, IL1↓, 2, IL6↓, 2, Imm↑, 1, Inflam↓, 2, MCP1/CCL2↓, 1, mPGES-1↓, 1, NF-kB↓, 7, NF-kB↑, 1, p65↓, 1, PD-L1↓, 1, PGE2↓, 4, TNF-α↓, 3,
Protein Aggregation(tgid=19) ⓘ
PP2A↑, 1,
Hormonal & Nuclear Receptors(tgid=20) ⓘ
AR↓, 2, CDK6↓, 2,
Drug Metabolism & Resistance(tgid=21) ⓘ
ABCG2↓, 1, BioAv↓, 4, BioAv↑, 1, BioEnh↑, 1, ChemoSen↑, 5, Dose↑, 1, Dose↝, 1, eff↓, 1, eff↑, 4, selectivity↑, 1,
Clinical Biomarkers(tgid=22) ⓘ
AFP↓, 1, AR↓, 2, BMPs↑, 1, EGFR↓, 4, EZH2↓, 1, FOXM1↓, 2, GutMicro↑, 1, IL6↓, 2, Ki-67↓, 1, Myc↓, 1, PD-L1↓, 1,
Functional Outcomes(tgid=23) ⓘ
AntiCan↑, 3, AntiTum↑, 2, chemoP↑, 2, neuroP↑, 1, OS↑, 1, PRAS40↑, 1, RenoP↑, 1, toxicity↓, 2, toxicity↝, 1,
Total Targets: 261
Pathway results for Effect on Normal Cells:
NA, unassigned(tgid=0) ⓘ
AntiArt↑, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↓, 1, antiOx↑, 4, Catalase↑, 3, GPx↑, 3, GSH↑, 1, HO-1↑, 3, lipid-P↓, 2, NRF2↑, 3, ROS↓, 8, SOD↑, 2,
Mitochondria & Bioenergetics(tgid=3) ⓘ
MMP↑, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
ALAT↓, 1, AMPK↑, 1, GlutMet↑, 1, SIRT1↑, 2,
Cell Death(tgid=5) ⓘ
Akt↑, 1, Casp1↓, 1, Casp3↓, 2, iNOS↓, 2, p‑JNK↓, 1, p38↓, 1,
Transcription & Epigenetics(tgid=7) ⓘ
other↑, 1,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
GSK‐3β↓, 1, GSK‐3β↑, 1, PI3K↑, 1,
Migration(tgid=13) ⓘ
5LO↓, 2, MMP13↓, 1, MMP2↓, 1, MMP3↓, 5, MMP9↓, 2,
Angiogenesis & Vasculature(tgid=14) ⓘ
NO↓, 3, NO↑, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
COX1↓, 1, COX2/PTGS2↓, 5, IL1↓, 1, IL10↓, 1, IL12↓, 1, IL1β↓, 1, IL2↑, 1, IL6↓, 4, IL8↓, 1, Inflam↓, 4, IκB?, 1, MCP1/CCL2↓, 1, NF-kB↓, 4, PGE2↓, 5, PGE2↑, 1, Th1 response↓, 1, Th2↑, 2, TNF-α↓, 4,
Synaptic & Neurotransmission(tgid=18) ⓘ
tau↓, 1,
Protein Aggregation(tgid=19) ⓘ
NLRP3↓, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 2, BioAv↑, 1, BioAv↝, 1, Half-Life↓, 1,
Clinical Biomarkers(tgid=22) ⓘ
ALAT↓, 1, AST↓, 1, IL6↓, 4,
Functional Outcomes(tgid=23) ⓘ
AntiAge↑, 1, AntiCan↑, 2, cardioP↑, 2, cognitive↑, 2, hepatoP↑, 1, memory↑, 1, neuroP↓, 1, neuroP↑, 5, toxicity∅, 1,
Total Targets: 69
Scientific Paper Hit Count for: MMP3, Matrix metalloproteinase-3
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#:757 State#:% Dir#:1
wNotes=on sortOrder:rid,rpid
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