ATG5 Cancer Research Results
ATG5, Autophagy-related 5: Click to Expand ⟱
| Source: |
| Type: |
ATG5 (Autophagy-related 5) is a protein that plays a crucial role in the process of autophagy, a cellular mechanism that involves the degradation and recycling of damaged or dysfunctional cellular components. ATG5 is a key component of the autophagy machinery and is involved in the formation of autophagosomes, which are double-membraned vesicles that engulf and digest cellular components.
Increased expression in: breast, GBM (poor prognosis).
Decreased in: Colon, Prostate (associated with improved prognosis).
|
Scientific Papers found: Click to Expand⟱
| - |
vitro+vivo, |
ESCC, |
TE1 |
|
|
|
- |
vitro+vivo, |
ESCC, |
KYSE-510 |
|
|
|
- |
in-vitro, |
Nor, |
Het-1A |
|
|
|
TumCP↓,
LC3‑Ⅱ/LC3‑Ⅰ↑,
p62↓,
p‑AMPK↑,
mTOR↓,
TumAuto↑,
NCOA4↑,
MDA↑,
Iron↑, elevated malondialdehyde and Fe2+ production levels
TumW↓,
TumVol↓,
ATG5↑,
ATG7↑,
TfR1/CD71↓,
FTH1↓, suppressed the expression of ferritin heavy chain 1 (the major intracellular iron-storage protein)
ROS↑,
Iron↑,
Ferroptosis↑,
*toxicity↓, 80 μg/mL allicin for 24 h did not change the viability of Het-1A cells. A slight reduction in cell viability was observed when Het-1A cells were treated with 160 μg/mL allicin for 24 h
*Inflam↓, Phyllanthus emblica polysaccharides (PEP) exhibit anti-inflammatory, antioxidant, and gut microbiota-modulating properties in colitis and obese mice.
*antiOx↓,
*GutMicro↑,
*cognitive↑, In vivo results showed that PEP administration significantly alleviated cognitive decline by reducing neuroinflammatory cytokines (TNF-α, IL-6, and IL-1β) and MDA levels while increasing anti-inflammatory factors (IL-4 and IL-10) and antioxidants (S
*TNF-α↓,
*IL6↓,
*IL1β↓,
*MDA↓,
*IL4↑,
*IL10↑,
*TAC↑,
*ATG5↑, Mechanistically, PEP upregulated autophagy-related proteins (Atg5, Beclin1, and LC3B) and LRP1 expression while downregulating AD-related proteins (BACE1, APP, Aβ, and phospho-TauSer404)
*Beclin-1/ATG6↑,
*LC3B↑,
*LRP1↑,
*BACE/β-secretase↓,
*APP↓,
*Aβ↓,
*tau↓,
tumCV↓, Berbamine caused a remarkable decrease in the HT-29 cell viability with an IC50 of 14 µM, while the high IC50 of Berbamine against the normal CDD-18Co cells indicated low toxicity of this molecule against the normal cells.
selectivity↑,
Casp3↑, Berbamine also caused activation of caspase-3 and 9 and increased the Bax/Bcl-2 ratio.
Casp9↑,
Bax:Bcl2↑,
ATG5↑, increase in protein levels of LC3B-I, ATG-5, ATG-12 and Beclin-1.
Beclin-1/ATG6↑,
TumCP↓, Berbamine decreased the migration potential of the HT-29 and also blocked the MEK/ERK signalling pathway in colon cancer cells.
MEK↓,
ERK↓,
*Inflam↓, anticancer, anti-edema, anti-inflammatory, anti-microbial, anti-coagulant, anti-osteoarthritis, anti-trauma pain, anti-diarrhea, wound repair.
*Bacteria↓,
*Pain↓,
*Diar↓,
*Wound Healing↑,
ERK↓, Figure 1
JNK↓,
XIAP↓,
HSP27↓,
β-catenin/ZEB1↓,
HO-1↓,
lipid-P↓,
ACSL4↑,
ROS↑,
SOD↑,
Catalase↓,
GSH↓,
MDA↓,
Casp3↓,
Casp9↑,
DNAdam↑,
Apoptosis↑,
NF-kB↓,
P53↑,
MAPK↓,
APAF1↑,
Cyt‑c↓,
CD44↓,
Imm↑, Bromelain was also studied in the innate immune system, where it could enhance and sustain the process
ATG5↑,
LC3I↑,
Beclin-1/ATG6↑,
IL2↓, bromelain in vitro experiments resulted in diminished amounts of IL-2, IL-6, IL-4, G-CSF, Gm-CSF, IFN-γ,
IL4↓,
IFN-γ↓,
COX2/PTGS2↓, proprietary bromelain extract could decrease IL-8, COX-2, iNOS, and TNF-α without affecting cell viability.
iNOS↓,
ChemoSen↑, Bromelain may increase the cytotoxicity of cisplatin in the treatment of breast cancer as reported in 2 studies with MDA-MB-231 and 4T1 Breast Tumor cell lines
RadioS↑, The size and weight of tumors in gamma-irradiated EST-bearing mice treated with bromelain decreased significantly with a significant amelioration in the histopathological examination
Dose↝, oral bromelain administration in breast cancer patients (daily up to a dose of 7800 mg)
other↓, The role of bromelain (in combination with papain, sodium selenite and Lens culinaris lectin) has been also tested as a complementary medicine on more than 600 breast cancer patients to reduce the side effects caused by the administration of the adju
AntiCan↑, Bromelain, an extract of pineapple, was shown to have anticancer effects
TumCG↓, bromelain inhibited CRC cell growth in cell lines and tumor growth in the zebrafish and xenograft mouse models.
ROS↑, induced high levels of ROS and superoxide, plus autophagosome and lysosome formation.
Apoptosis↑, High levels of apoptosis were also induced, which were associated with elevated amounts of apoptotic proteins like apoptotic induction factor, Endo G, and caspases-3, -8, and -9
Endoglin↑,
Casp3↑,
Casp8↑,
Casp9↑,
ATG5↑, increases in levels of ATG5/12, beclin, p62, and LC3 conversion rates were found after bromelain treatment.
Beclin-1/ATG6↑,
p62↑,
PARP↑, Levels of cleaved caspase-3, caspase-8, caspase-9, and poly(ADP ribose) polymerase (PARP)-1 increased after bromelain exposure.
TumCG↓, Exposure to capsaicin inhibited cancer cell growth and increased G1 phase cell cycle arrest.
TumCCA↑,
TumAuto↑, induced autophagy via involvement of the class III PI3K/Beclin-1/Bcl-2 signaling pathway.
Casp3↑, increasing caspase-3 activity to induce apoptosis
Ca+2↑, involves increased intracellular Ca2+ levels [19,24], the generation of reactive oxygen species
ROS↑,
MMP↓, disruption of mitochondrial membrane potential
LC3‑Ⅱ/LC3‑Ⅰ↑, Capsaicin Upregulates LC3-II and Atg5 Expression and Downregulates p62 and Fap-1 Expression in NPC-TW01 Cells
ATG5↑,
p62↓,
Fap1↓,
PI3K↓, Capsaicin Inhibits PI3K Expression and the Phosphorylation of Downstream Effectors of the PI3K/Akt/mTOR Pathway in NPC-TW01 Cells
DNAdam↑, have found that capsaicin may induce DNA and chromosomal damage in human lung (A549) and prostate (DU145) cancer cells
chemoPv↑, Capsaicin has shown significant prospects as an effective chemopreventive agent
Ca+2↑, Capsaicin was shown to cause upstream activation of Ca2+
antiOx↑, Another plausible mechanism implicated in the chemopreventive action of capsaicin is its anti-oxidative effects.
*ROS↓, capsaicin inhibits ROS release and the subsequent mitochondrial membrane potential collapse, cytochrome c expression, chromosome condensation, and caspase-3 activation induced by oxidized low-density lipoprotein in normal human HUVEC cells
*MMP∅,
*Cyt‑c∅,
*Casp3∅,
*eff↑, dietary curcumin and capsaicin concurrent administration in high-fat diet-fed rats were shown to mitigate the testicular and hepatic antioxidant status by increasing GSH levels, glutathione transferase activity, and Cu-ZnSOD expression
*Inflam↓, Anti-inflammation is another mechanism implicated in the chemopreventive action of capsaicin.
*NF-kB↓, inhibition of NF-kB by capsaicin
*COX2/PTGS2↓, compound elicits COX-2 enzyme activity inhibition and downregulation of iNOS
iNOS↓,
TRPV1↑, major pro-apoptotic mechanisms of capsaicin is via the vanilloid receptors, primarily TRPV1
i-Ca+2?, causing a concomitant influx of Ca2+: severe condition of mitochondria calcium overload. at high concentration (> 10 µM), capsaicin induces a slow but persistent increase in intracellular Ca2+
MMP↓, depolarization of mitochondria membrane potential
Cyt‑c↑, release of cytochrome C
Bax:Bcl2↑, activation of Bax and p53 through C-jun N-terminal kinase (JNK) activation
P53↑,
JNK↑,
PI3K↓, blocking the Pi3/Akt/mTOR signalling pathway, capsaicin increases levels of autophagic markers (LC3-II and Atg5)
Akt↓,
mTOR↓,
LC3II↑,
ATG5↑,
p62↑, enhances p62 and Fap-1 degradation and increases caspase-3 activity to induce apoptosis in human nasopharyngeal carcinoma cells
Fap1↓,
Casp3↑,
Apoptosis↑,
ROS↑, generation of ROS in human hepatoma (HepG2 cells)
MMP9↓, inhibition of MMP9 by capsaicin occurs via the suppression of AMPK-NF-κB, EGFR-mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP-1 signaling pathway
eff↑, capsaicin 8% patch could promote the regeneration and restoration of skin nerve fibres in chemotherapy-induced peripheral neuropathy in addition to pain relief
eff↓, capsaicin has shown several unpleasant side effects, including stomach cramps, skin and gastric irritation, and burning sensation
eff↑, liposomes and micro-emulsion-based drugs have been known to significantly improve oral bioavailability and reduce the irritation of drugs
selectivity↑, In addition, these delivery systems can be surfaced-modified to perform site-directed/cell-specific drug delivery, thereby ensuring increased cell death of cancer cells while sparing non-selective normal cells
eff↑, Furthermore, owing to its antioxidant potential, capsaicin has been applied as a bioreduction and capping agent to synthesize biocompatible silver nanoparticles
ChemoSen↑, capsaicin has been combined with other anticancer therapies for more pronounced anticancer effects
| - |
in-vitro, |
Pca, |
PC3 |
|
|
|
- |
in-vivo, |
PC, |
NA |
|
|
|
- |
in-vitro, |
Pca, |
LNCaP |
|
|
|
- |
in-vitro, |
Pca, |
WPMY-1 |
|
|
|
Apoptosis↑,
Ca+2↓, Ca2+-chelating property of citrate
Akt↓, downregulation CaMKII/AKT/mTOR pathway
mTOR↓,
selectivity↑, citrate (0-3 mM) did not affect the cell growth of normal prostate epithelial cells (WPMY-1).
TumCP↓, also verified that citrate significantly inhibited the proliferation of PCa cells (PC3 and LNCaP).
cl‑Casp3↑,
cl‑PARP↑, increased the levels of Cleaved caspase3 and Cleaved PARP in prostate cancer cells
LC3‑Ⅱ/LC3‑Ⅰ↑, ratio of LC3-II/I was markedly increased and the expression of p62 was significantly decreased after the treatment of citrate in PCa cells (PC3 and LNCaP).
p62↓,
ATG5↑, citrate also promoted the protein expression of Atg5, Atg7 and Beclin-1 in PCa cells (PC3 and LNCaP).
ATG7↑,
Beclin-1/ATG6↑,
TumAuto↑, citrate induces autophagy of prostate cancer cells
CaMKII
↓, citrate suppresses the activation of the CaMKI
| - |
in-vitro, |
GC, |
SGC-7901 |
|
|
|
- |
in-vitro, |
GC, |
BGC-823 |
|
|
|
TumCP↓,
Apoptosis↑,
TumAuto↑,
P53↑,
PI3K↓,
P21↑,
p‑Akt↓,
p‑mTOR↓,
Bcl-2↓,
Bcl-xL↓,
LC3I↓, LC3I
BAX↑,
Beclin-1/ATG6↑,
cl‑Casp3↑,
cl‑PARP↑,
LC3II↑,
ATG3↑,
ATG5↑,
| - |
Review, |
Var, |
NA |
|
|
|
- |
Review, |
AD, |
NA |
|
|
|
Beclin-1/ATG6↑, EGCG not only regulates autophagy via increasing Beclin-1 expression and reactive oxygen species generation,
ROS↑,
Apoptosis↑, Apoptosis is a common cell function in biology and is induced by endoplasmic reticulum stress (ERS)
ER Stress↑,
*Inflam↓, EGCG has health benefits including anti-tumor [15], anti-inflammatory [16], anti-diabetes [17], anti-myocardial infarction [18], anti-cardiac hypertrophy [19], anti-atherosclerosis [20], and antioxidant
*cardioP↑,
*antiOx↑,
*LDL↓, These effects are mainly related to (LDL) cholesterol inhibition, NF-κB inhibition, MPO activity inhibition, decreased levels of glucose and glycated hemoglobin in plasma, decreased inflammatory markers, and reduced ROS generation
*NF-kB↓,
*MPO↓,
*glucose↓,
*ROS↓,
ATG5↑, EGCG induced autophagy by enhancing Beclin-1, ATG5, and LC3B and promoted mitochondrial depolarization in breast cancer cells.
LC3B↑,
MMP↑,
lactateProd↓, 20 mg kg−1 EGCG significantly decreased glucose, lactic acid, and vascular endothelial growth factor (VEGF) levels
VEGF↓,
Zeb1↑, (20 uM) inhibited the proliferation through activating autophagy via upregulating ZEB1, WNT11, IGF1R, FAS, BAK, and BAD genes and inhibiting TP53, MYC, and CASP8 genes in SSC-4 human oral squamous cells [
Wnt↑,
IGF-1R↑,
Fas↑,
Bak↑,
BAD↑,
TP53↓,
Myc↓,
Casp8↓,
LC3II↑, increasing the LC3-II expression levels and induced apoptosis via inducing ROS in mesothelioma cell lines,
NOTCH3↓, but also could reduce partially Notch3/DLL3 to reduce drug-resistance and the stemness of tumor cells
eff↑, In combination therapies, low-intensity pulsed electric field (PEF) can improve EGCG to affect tumor cells; ultrasound (US) with tumor cells is the application of physical stimulation in cancer therapy.
p‑Akt↓, 20 μM EGCG increased intracellular ROS levels and LC3-II, and inhibited p-Akt in PANC-1 cells
PARP↑, 100 μM EGCG increased LC3-II, activated caspase-3 and PARP, and reduced p-Akt in HepG2
*Cyt‑c↓, EGCG protected neuronal cells against human viruses by inhibiting cytochrome c and Bax translocations, and reducing autophagy with increased LC3-II expression and decreased p62 expression
*BAX↓,
*memory↑, EGCG restored autophagy in the mTOR/p70S6K pathway to weaken memory and learning disorders induced by CUMS
*neuroP↑, Finally, EGCG increased the neurological scores through inhibiting cell death
*Ca+2?, EGCG treatment, [Ca2+]m and [Ca2+]i expressions were reduced and oxyhemoglobin-induced mitochondrial dysfunction lessened.
GRP78/BiP↑, MMe cells with EGCG treatment improved GRP78 expression in the endoplasmic reticulum, and induced EDEM, CHOP, XBP1, and ATF4 expressions, and increased the activity of caspase-3 and caspase-8.
CHOP/DDIT3↑, GRP78 accumulation converted UPR of MMe cells into pro-apoptotic ERS
ATF4↑,
Casp3↑,
Casp8↑,
UPR↑,
*antiOx↑, effective antioxidant, anti-inflammatory
*Inflam↓,
neuroP↑, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential.
hepatoP↑,
RenoP↑,
cycD1/CCND1↓, Figure 3
TumCCA↑,
MMPs↓,
VEGF↓,
MAPK↓,
NF-kB↓,
angioG↓,
Beclin-1/ATG6↑,
LC3s↑,
ATG5↑,
Bcl-2↓,
BAX↑,
Casp↑,
TNF-α↓,
Half-Life↓, Fisetin was given at an effective dosage of 223 mg/kilogram intraperitoneally in mice. The plasma concentration declined biophysically, with a rapid half-life of 0.09 h and a terminal half-life of 3.1 h,
MMP↓, Fisetin powerfully improved apoptotic cells and caused the depolarization of the mitochondrial membrane.
mt-ROS↑, Fisetin played a role in the induction of apoptosis, independently of p53, and increased mitochondrial ROS generation.
cl‑PARP↑, fisetin-induced sub-G1 population as well as PARP cleavage.
CDK2↓, Moreover, the activities of cyclin-dependent kinases (CDK) 2 as well as CDK4 were decreased by fisetin and also inhibited CDK4 activity in a cell-free system, demonstrating that it might directly inhibit the activity of CDK4
CDK4↓,
Cyt‑c↑, Moreover, release of cytochrome c and Smac/Diablo was induced by fisetin
Diablo↑,
DR5↑, Fisetin caused an increase in the protein levels of cleaved caspase-8, DR5, Fas ligand, and TNF-related apoptosis-inducing ligand
Fas↑,
PCNA↓, Fisetin decreased proliferation-related proteins such as PCNA, Ki67 and phosphorylated histone H3 (p-H3) and decreased the expression of cell growth
Ki-67↓,
p‑H3↓,
chemoP↑, Paclitaxel treatment only showed more toxicity to normal cells than the combination of flavonoids with paclitaxel, suggesting that fisetin might bring some safety against paclitaxel-facilitated cytotoxicity.
Ca+2↑, Fisetin encouraged apoptotic cell death via increased ROS and Ca2+, while it increased caspase-8, -9 and -3 activities and reduced the mitochondrial membrane potential in HSC3 cells.
Dose↝, After fisetin treatment at 40 µM, invasion was reduced by 87.2% and 92.4%, whereas after fisetin treatment at 20 µM, invasion was decreased by 52.4% and 59.4% in SiHa and CaSki cells, respectively
CDC25↓, This study proposes that fisetin caused the arrest of the G2/M cell cycle via deactivating Cdc25c as well Cdc2 via the activation of Chk1, 2 and ATM
CDC2↓,
CHK1↑,
Chk2↑,
ATM↑,
PCK1↓, fisetin decreases the levels of SOS-1, pEGFR, GRB2, PKC, Ras, p-p-38, p-ERK1/2, p-JNK, VEGF, FAK, PI3K, RhoA, p-AKT, uPA, NF-ĸB, MMP-7,-9 and -13, whereas it increases GSK3β as well as E-cadherin in U-2 OS
RAS↓,
p‑p38↓,
Rho↓,
uPA↓,
MMP7↓,
MMP13↓,
GSK‐3β↑,
E-cadherin↑,
survivin↓, whereas those of survivin and BCL-2 were reduced in T98G cells
VEGFR2/KDR/Flk1↓, Fisetin inhibited the VEGFR expression in Y79 cells as well as the angiogenesis of a tumor.
IAP2/BIRC3↓, The downregulation of cIAP-2 by fisetin
STAT3↓, fisetin induced apoptosis in TPC-1 cells via the initiation of oxidative damage and enhanced caspases expression by downregulating STAT3 and JAK 1 signaling
JAK1↓,
mTORC1↓, Fisetin acts as a dual inhibitor of mTORC1/2 signaling,
mTORC2↓,
NRF2↑, Moreover, In JC cells, the Nrf2 expression was gradually increased by fisetin from 8 h to 24 h
chemoPv↑, Both crude extracts and pure compounds of the plant were reported to induce chemoprevention, selective cytotoxicity, cell cycle arrest, apoptosis, autophagy and anti-metastasis effects in varied types of human cancer cells.
selectivity↑,
TumCCA↑,
Apoptosis↑,
TumAuto↑,
TumMeta↓,
ATG5↑, figure 3
Beclin-1/ATG6↑,
LC3II↑,
MMP2↓,
MMP9↓,
CD31/PECAM-1↓,
VEGF↓,
uPA↓,
TIMP2↑,
NF-kB↓,
p38↑,
P53↑,
Casp3↑,
Casp8↑,
Casp9↑,
Bcl-2↓,
BAX↑,
Cyt‑c↑,
TNF-α↑,
Fas↑,
FasL↑,
JNK↑,
cJun↑,
angioG↓,
VEGFR2/KDR/Flk1↓,
PCNA↓,
CCN2/CTGF↓,
RAGE↓,
| - |
in-vitro, |
Melanoma, |
A375 |
|
|
|
cl‑Casp↑, Our results revealed that both HLP and ECG induced the caspases cleavages, Bcl-2 family proteins regulation, and Fas/FasL activation in A375 cells.
Bcl-2↓,
Fas↑,
FasL↑,
ATG5↑, HLP could increase the expressions of autophagy-related proteins autophagy-related gene 5 (ATG5), Beclin1, and light chain 3-II (LC3-II), and induce autophagic cell death in A375 cells.
Beclin-1/ATG6↑,
LC3B-II↑,
TumAuto↑,
TumCCA↑, induction of G0/G1 and G2/M cell cycle arrest
CDK2↓, (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins),
EMT↓, epithelial–mesenchymal transition inhibition via the downregulation of mesenchymal markers
MMPs↓, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases
AMPK↑, (activation of 5′ AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling)
TumCI↓, inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)
TumCMig↓,
TumMeta↓,
VEGFR2/KDR/Flk1↓,
*antiOx↑, diverse biological activities, including anti-arrhythmic, anti-inflammatory, anti-oxidative, anti-depressant, anti-thrombocytic, and anxiolytic activities
*Inflam↓,
*BBB↑, Due to its ability to cross the blood–brain barrier
*neuroP↑, beneficial towards neuronal protection through various mechanism, such as the preservation of Na+/K+ ATPase, phosphorylation of pro-survival factors, preservation of mitochondria, prevention of glucose, reactive oxgen species (ROS), and inflammatory
*ROS↓,
Dose↝, Generally, the concentrations used for the in vitro studies are between 0–150 μM
selectivity↑, Interestingly, honokiol has been shown to exhibit minimal cytotoxicity against on normal cell lines, including human fibroblast FB-1, FB-2, Hs68, and NIH-3T3 cells
Casp3↑, ↑ Caspase-3 & caspase-9
Casp9↑,
NOTCH1↓, Inhibition of Notch signalling: ↓ Notch1 & Jagged-1;
cycD1/CCND1↓, ↓ cyclin D1 & c-Myc;
cMyc↓,
P21?, ↑ p21WAF1 protein
DR5↑, ↑ DR5 & cleaved PARP
cl‑PARP↑,
P53↑, ↑ phosphorylated p53 & p53
Mcl-1↑, ↓ Mcl-1 protein
p65↓, ↓ p65; ↓ NF-κB
NF-kB↓,
ROS↑, ↑ JNK activation ,Increase ROS activity:
JNK↑,
NRF2↑, ↑ Nrf2 & c-Jun protein activation
cJun↑,
EF-1α↓, ↓ EFGR; ↓ MAPK/PI3K pathway activity
MAPK↓,
PI3K↓,
mTORC1↓, ↓ mTORC1 function; ↑ LKB1 & cytosolic localisation
CSCs↓, Inhibit stem-like characteristics: ↓ Oct4, Nanog & Sox4 protein; ↓ STAT3;
OCT4↓,
Nanog↓,
SOX4↓,
STAT3↓,
CDK4↓, ↓ Cdk2, Cdk4 & p-pRbSer780;
p‑RB1↓,
PGE2↓, ↓ PGE2 production ↓ COX-2 ↑ β-catenin
COX2/PTGS2↓,
β-catenin/ZEB1↑,
IKKα↓, ↓ IKKα
HDAC↓, ↓ class I HDAC proteins; ↓ HDAC activity;
HATs↑, ↑ histone acetyltransferase (HAT) activity; ↑ histone H3 & H4
H3↑,
H4↑,
LC3II↑, ↑ LC3-II
c-Raf↓, ↓ c-RAF
SIRT3↑, ↑ Sirt3 mRNA & protein; ↓ Hif-1α protein
Hif1a↓,
ER Stress↑, ↑ ER stress signalling pathway activation; ↑ GRP78,
GRP78/BiP↑,
cl‑CHOP/DDIT3↑, ↑ cleaved caspase-9 & CHOP;
MMP↓, mitochondrial depolarization
PCNA↓, ↓ cyclin B1, cyclin D1, cyclin D2 & PCNA;
Zeb1↓, ↓ ZEB2
Inhibit
NOTCH3↓, ↓ Notch3/Hes1 pathway
CD133↓, ↓ CD133 & Nestin protein
Nestin↓,
ATG5↑, ↑ Atg7 protein activation; ↑ Atg5;
ATG7↑,
survivin↓, ↓ Mcl-1 & survivin protein
ChemoSen↑, honokiol potentiated the apoptotic effect of both doxorubicin and paclitaxel against human liver cancer HepG2 cells.
SOX2↓, Honokiol was shown to downregulate the expression of Oct4, Nanog, and Sox2 which were known to be expressed in osteosarcoma, breast carcinoma and germ cell tumours
OS↑, Lipo-HNK was also shown to prolong survival and induce intra-tumoral apoptosis in vivo.
P-gp/ABCB1↓, Honokiol was shown to downregulate the expression of P-gp at mRNA and protein levels in MCF-7/ADR, a human breast MDR cancer cell line
Half-Life↓, For i.v. administration, it has been found that there was a rapid rate of distribution followed by a slower rate of elimination (elimination half-life t1/2 = 49.22 min and 56.2 min for 5 mg or 10 mg of honokiol, respectively
Half-Life↝, male and female dogs was assessed. The elimination half-life (t1/2 in hours) was found to be 20.13 (female), 9.27 (female), 7.06 (male), 4.70 (male), and 1.89 (male) after administration of doses of 8.8, 19.8, 3.9, 44.4, and 66.7 mg/kg, respectively.
eff↑, Apart from that, epigallocatechin-3-gallate functionalized chitin loaded with honokiol nanoparticles (CE-HK NP), developed by Tang et al. [224], inhibit HepG2
BioAv↓, extensive biotransformation of honokiol may contribute to its low bioavailability.
| - |
in-vitro, |
OS, |
U2OS |
|
|
|
- |
in-vivo, |
NA, |
NA |
|
|
|
TumCD↑, honokiol caused dose-dependent and time-dependent cell death in human osteosarcoma cells
TumAuto↑, death induced by honokiol were primarily autophagy and apoptosis.
Apoptosis↑,
TumCCA↑, honokiol induced G0/G1 phase arrest,
GRP78/BiP↑, elevated the levels of glucose-regulated protein (GRP)−78, an endoplasmic reticular stress (ERS)-associated protein
ROS↑, increased the production of intracellular reactive oxygen species (ROS)
eff↓, In contrast, reducing production of intracellular ROS using N-acetylcysteine, a scavenger of ROS, concurrently suppressed honokiol-induced cellular apoptosis, autophagy, and cell cycle arrest.
p‑ERK↑, honokiol stimulated phosphorylation of extracellular signal-regulated kinase (ERK)1/2.
selectivity↑, human fibroblasts showed strong resistance to HNK, the IC50 values for which were 118.9 and 71.5 μM
Ca+2↑, HNK increased intracellular Ca2+ in both HOS and U2OS cells
MMP↓, mitochondrial membrane potential (MMP) sharply decreased following HNK treatment
Casp3↑, HNK markedly activated caspase-3, caspase-9
Casp9↑,
cl‑PARP↑, led to PARP cleavage
Bcl-2↓, expression of Bcl-2, Bcl-xl, and survivin was found to be decreased
Bcl-xL↓,
survivin↓,
LC3B-II↑, HNK increased the level of LC3B-II and Atg5 in HOS and U2OS cells.
ATG5↑,
TumVol↓, HNK at doses of 40 mg/kg resulted in significant decrease in tumor volume and weight, after 7 days of drug administration
TumW↓,
ER Stress↑, ER stress can trigger ROS production through release of calcium
| - |
in-vitro, |
Liver, |
HepG2 |
|
|
|
- |
in-vitro, |
Liver, |
HUH7 |
|
|
|
tumCV↓, ISO exposure inhibited cell viability and colony growth, activated apoptotic pathway, and triggered dysregulated autophagy by activating the AMPK/mTOR/p70S6K pathway.
Apoptosis↑,
TumAuto↑, Isoquercitrin induces autophagy in HCC cells
AMPK↑,
TumCG↓, Isoquercitrin inhibits HCC cell growth
ATG5↑, dose-dependent increase in LC3, Atg5, and Beclin-1, and a decrease in p62/sequestosome-1 (p62) expression, in HepG2 and Huh7 cells treated with ISO for 48 h
Beclin-1/ATG6↑,
p‑mTOR↓, As expected, ISO treatment led to dose-dependent activation of AMPK and decreased the phosphorylation of mTOR and its downstream substrate p70/p85S6 kinase (p70/p85S6K)
Casp3↑, ISO actions were characterized by up-regulation of active caspase-3 and cleaved PARP and increased Bax/Bcl-2 ratio, indicative of apoptosis, concomitant with enhanced LC3-II expression and p62 degradation, reflecting induction of autophagy
cl‑PARP↑,
Bax:Bcl2↑,
LC3II↑,
p62↓,
| - |
NA, |
neuroblastoma, |
SH-SY5Y |
|
|
|
*toxicity↑, Ivermectin (IVM) could cause potential neurotoxicity; however, the precise molecular mechanisms remain unclear.
TumCD↑, The results show that IVM treatment (2.5–15 μM) for 24 h could induce dose-dependent cell death in SH-SY5Y cells.
ROS↑, Compared to the control, IVM treatment significantly promoted the production of ROS, mitochondrial dysfunction, and cell apoptosis.
mtDam↑,
Apoptosis↑,
MitoP↑, IVM treatment also promoted mitophagy and autophagy, which were charactered by the decreased expression of phosphorylation (p)-Akt and p-mTOR proteins, increased expression of LC3II, Beclin1, ATG5, PINK, and Pakin1 proteins and autophagosome formatio
TumAuto↑,
p‑Akt↓,
p‑mTOR↓,
LC3II↑,
Beclin-1/ATG6↑,
ATG5↑,
PINK1↑,
PARK2↑,
tumCV↓, At 6 h and 12 h, IVM treatment at 15 μM significantly decreased the cell viabilities to 44.3% and 35.6% (both p < 0.01), respectively;
MDA↑, IVM treatment at the doses of 10 and 15 μM significantly increased the levels of MDA to 0.25 nmol/mg and 0.76 nmol/mg protein (both p < 0.01) (Figure 3B), respectively; increased the activities of SOD to 1.61 U/mg and 3.48 U/mg protein (both p < 0.
SOD↑,
Catalase↑,
eff↓, NAC treatment at 10 mM significantly inhibited the IVM-induced production of ROS
MMP↓, IVM treatment significantly decreased the ΔΨm in a dose-dependent manner.
BAX↑, IVM treatment significantly increased the expressions of Bax, cleaved caspase-3, cleaved caspase-9, cleaved PARP-1 proteins, and CytC proteins, and decreased the expressions of Bcl-2 and pro-caspase-3 proteins.
cl‑Casp3↑,
cl‑Casp9↑,
cl‑PARP↑,
Cyt‑c↑,
Bcl-2↓,
proCasp3↓,
Bax:Bcl2↑, IVM treatment at 10 μM significantly increased the ratio of Bax/Bcl-2 to 2.6-fold
eff↑, Inhibition of Autophagy Improves Ivermectin-Induced Cytotoxicity, Oxidative Stress, and Apoptotic Cell Death
*AntiP↑, IVM has been widely used as an antiparasitic drug in human and veterinary medicines
*Inflam↓, IVM exhibited several new threptic effects, including anti-cancer, anti-inflammation, anti-diabetic, and antiviral effects
*AntiDiabetic↑,
*AntiViral↑,
BBB∅, In relation to the current recommended dose, IVM is not thought to readily cross the blood–brain barrier in humans
toxicity↝, It has been reported that an IVM overdose could induce neurotoxicity in SARS-CoV-2 patients and the main neurotoxic symptoms include confusion, ataxia, weakness, hypotension, and seizures
Akt↓, inhibition by IVM of the Akt/mTOR pathway to induce autophagy and p-21-activated kinase 1(PAK1)was the target of IVM for breast cancer
mTOR↓,
TumAuto↑,
TumCP↓, IVM could inhibit the proliferation of the canine breast tumor cell lines CMT7364 and CIPp by blocking the cell cycle without increasing apoptosis, and the mechanism of IVM may be related to the inhibition of the Wnt pathway
TumCCA↑,
Wnt↓,
YAP/TEAD↓,
MMP↓, IVM could significantly reduce the mitochondrial membrane potential and inhibit mitochondrial respiration and ATP production.
mitResp↓,
ATP↓,
eff↓, acetyl-L-cysteine (NAC), could reverse IVM-induced inhibition
eff↑, it was found that IVM could enhance the drug activity of the anti-androgen drug enzalutamide in the prostate cancer cell line LNCaP and reverse the resistance of the prostate cancer cell line PC3 to docetaxel
ROS↑, induction of reactive oxygen species (ROS) production.
ChemoSen↑, IVM can enhance the efficacy of cisplatin to improve the treatment of epithelial ovarian cancer, and the mechanism is related to the inhibition of the Akt/mTOR pathway
PAK1↓, IVM also had a cytotoxic effect on a variety of nasopharyngeal cancer cells in vitro, and the mechanism is related to the reduction of PAK1 kinase activity to inhibit the MAPK pathway.
MAPK↓,
EMT↓, IVM could reduce the metastasis of lung cancer cells by inhibiting EMT.
Beclin-1/ATG6↑, IVM in the breast cancer cell lines MCF-7 and MDA-MB-231 significantly increased intracellular autophagic flux and the expression of key autophagy proteins such as LC3, Bclin1, Atg5
ATG5↑,
CSCs↓, Further studies showed that IVM could inhibit CSCs by regulating the PAK1-STAT3 axis
STAT3↝,
P-gp/ABCB1↓, Several studies have confirmed that IVM could reverse drug resistance by inhibiting P-gp and MDR-associated proteins
MDR1↓,
HSP27↓, Inhibit HSP27 Prostate cancer, Lung cancer Colorectal cancer
Chl↑, Activate chloride channels Leukemia
TFE3↑, Increase TFE3 Activity Melanoma
TumCG↓, we showed that IV significantly suppressed the growth of liver cancer cells
Apoptosis↑, IV induced apoptosis by the mitochondrial apoptotic pathway, as evidenced by the increase of Bax, cleaved Caspase-3, poly (ADP-ribose) polymerase (PARP), and cytoplasm Cyto-c released from mitochondria.
BAX↑,
cl‑Casp3↑,
cl‑PARP↑,
Cyt‑c↑,
TumAuto↑, IV resulted in autophagy in liver cancer cells, supported by the enhancement of LC3II, autophagy-related protein (Atg) 3, Atg5 and Beclin1.
LC3II↑,
ATG3↑,
ATG5↑,
Beclin-1/ATG6↑,
ER Stress↑, IV was found to cause endoplasmic reticulum (ER) stress in liver cancer cells, along with the promotion of ER stress-related molecules, including inositol-requiring enzyme 1α (IRE1α), X-box-binding protein-1s (XBP-1s), C/EBP homologous protein (CHO
IRE1↑,
XBP-1↑,
CHOP/DDIT3↑,
GRP78/BiP↑, and glucose-regulated protein (GRP)-78
*chemoPv↑, IV could therefore be a strong candidate for liver cancer prevention.
| - |
in-vitro, |
HCC, |
HepG2 |
|
|
|
- |
in-vitro, |
HCC, |
HUH7 |
|
|
|
TumAuto↑, Kaempferol induced autophagy in a concentration- and time-dependent manner in HepG2 or Huh7 cells
ER Stress↑, kaempferol can induce autophagy via endoplasmic reticulum (ER) stress pathway.
CHOP/DDIT3↓, Our results demonstrated that kaempferol induced hepatocarcinoma cell death via ER stress and CHOP-autophagy signaling pathway;
chemoPv↑, kaempferol may be used as a potential chemopreventive agent for patients with hepatocellular carcinoma.
RadioS↑, kaempferol increased the effects of radiation on tumor cell killing in vitro and in vivo through inhibition of AKT/PI3K and ERK pathways
Akt↓,
PI3K↓,
ERK↓,
ATG5↑, HepG2 cells and Huh 7 cells treated with Kaempferol increased the protein levels of Atg5, Atg7, Beclin1
ATG7↑,
Beclin-1/ATG6↑,
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, |
BC, |
4T1 |
|
|
|
- |
in-vitro, |
Ovarian, |
OVCAR-3 |
|
|
|
- |
in-vitro, |
Ovarian, |
SKOV3 |
|
|
|
TumCP↓, Here, we show that citral inhibits proliferation of multiple human cancer cell lines.
TumCCA↑, In p53 expressing ECC-1 and OVCAR-3 but not in p53-deficient SKOV-3 cells, citral induces G1/S cell cycle arrest and apoptosis
Apoptosis↑,
cl‑Casp3↑, increased cleaved caspase3 and Bax and decreased Bcl-2.
BAX↑,
Bcl-2↓,
ER Stress↑, In SKOV-3 cells, citral induces the ER stress markers CHOP, GADD45, EDEM, ATF4, Hsp90, ATG5, and phospho-eIF2α.
CHOP/DDIT3↑,
GADD45A↑,
EDEM↑,
ATF4↑,
HSP90↑,
ATG5↑,
eIF2α↑,
ROS↑, Citral increases intracellular oxygen radicals and this leads to activation of p53
P53↑,
eff↓, Pretreatment with N-acetylcysteine NAC decreases phosphorylation of p53 in citral-treated ECC-1 and OVCAR-3.
| - |
in-vivo, |
Lung, |
A549 |
|
|
|
- |
in-vitro, |
Lung, |
A549 |
|
|
|
TumCG↓,
miR-486↑, decreased expression of miR-486 and an increased expression of BCAP were found in tumor tissues of lung cancer patients
BCAP↓,
Apoptosis↑,
ROS↑,
TumAuto↑, miR-486 is required for LF-MFs triggered autophagy
LC3II↑,
ATG5↑,
Beclin-1/ATG6↑,
p62↑, blocked p62 degradation
TumCP↓,
tumCV↓, Parthenolide inhibits HeLa cell viability in a dose dependent-manner and was confirmed by MTT assay.
TumAuto↑, Parthenolide (6 µM) induces mitochondrial-mediated apoptosis and autophagy by activation of caspase-3, upregulation of Bax, Beclin-1, ATG5, ATG3
Casp3↑,
BAX↑,
Beclin-1/ATG6↑,
ATG3↑,
ATG5↑,
Bcl-2↓, and down-regulation of Bcl-2 and mTOR
mTOR↓,
PI3K↓, inhibits PI3K and Akt expression through activation of PTEN expression.
Akt↓,
PTEN↑,
ROS↑, parthenolide induces generation of reactive oxygen species that leads to the loss of mitochondrial membrane potential
MMP↓,
*Dose↝, Though rutin is widely distributed in plants, buckwheat is considered as its major source
*BioAv↓, Rutin is not easily absorbed into the blood, since its sugar moiety blocks its passage through the intestinal epithelial layers, indicating its poor bioavailability compared to other flavonoid glycosides
*BioAv↓, several in vitro studies have reported the biodegradation of rutin by both intestinal and non-intestinal microorganisms including Pediococcus Q-05 (Kim et al. 1998), Cunninghamella echinulata ATCC 9244 (Araujo et al. 2013),
*BioAv↓, P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1) located in the intestine expelled rutin out of the cell thereby negatively affect its absorption and decrease its bioavailability (Zhang et al. 2013). This explains the significant role
*BioAv↓, The results showed that rutin was recovered as glucuronides and/or sulfates of quercetin and as unconjugated quercetin aglycone, but no free rutin was found in plasma, corroborating the pharmacokinetic studies of rutin in rats
*BioAv↝, All these studies strongly suggest that quercetin glucuronide is the major metabolite formed and circulated in blood after the intake of rutin.
TumCP↓, Rutin has been shown to hinder the proliferation of diverse cancer cell types in vitro, including breast, glioma, pancreas, colon, liver, lung, skin, prostate, cervical, and ovarian cancer cells
Risk↓, Rutin has been reported to prevent different types of cancers in vivo, such as breast, colon, melanoma, prostate, lymphoma, and leukemia.
*radioP↑, Recent reports showed that rutin has protective effects against radiation-induced inflammation and prevents radiation-induced skin carcinogenesis.
chemoPv↑, Overall, rutin exhibits outstanding chemopreventive and radioprotective effects both in vitro and in vivo,
TumCCA↑, Rutin has been reported to arrest cell cycle progression in cancer cells. Rutin can inhibit cell cycle at different checkpoints, such as G1, G2/M, and S phases.
GSK‐3β↑, Rutin can induce apoptosis in A549 lung cancer cells by upregulating the expression of GSK 3b, a downstream regulator of Wnt/b-catenin signaling
Wnt↓,
β-catenin/ZEB1↓,
ROS↑, Figure 3
BAX↑,
Casp3↑,
Casp8↑,
Casp9↑,
PARP↑,
Beclin-1/ATG6↑,
ATG5↑,
LC3II↑,
DNMT1↓,
P21↑,
CDK1↑,
CycB/CCNB1↓,
TNF-α↑,
VEGF↓,
IL1β↓,
NF-kB↓,
AP-1↓,
MYCN↓,
AMPK↑,
MAPK↓,
PI3K↓,
Akt↓,
cMET↓,
P-gp/ABCB1↓,
MRP1/ABCC1↓,
ABCG2↓,
MMPs↓,
TNF-α↓,
iNOS↓,
COX2/PTGS2↓,
angioG↓, Moreover, administration of 200 mM/kg rutin can inhibit angiogenesis in B16F-10 melanoma bearing C57BL/6 mice through the prevention of capillary formation
STAT3↓, rutin’s ability to prevent STAT3 activation mediated cancer development.
*chemoP↑, Several studies have reported that rutin can alleviate the toxicities induced by cisplatin, a platinum-based anticancer drug in experimental animal models
*ROS↓, The possible mechanisms by which rutin might exert its protective effects are ROS inhibition, suppression of MDA levels, and downregulation of p53, caspase-3, caspase-9, and JNK/TNF/p38 MAPK pathways
*MDA↓,
*P53↓,
*Casp3↓,
*Casp9↓,
*JNK↓,
*TNF-α↓,
*p38↓,
*MAPK↓,
GSH↓, GSH level in tumor cells was decreased after combined treatment with rutin, indicating that rutin sensitized cancer cells to cisplatin.
ChemoSen↑,
*hepatoP↑, rutin could inhibit cyclophosphamide-induced hepatocytotoxicity, probably through the upregulation of antioxidant enzyme activities and downregulation of serum toxicity markers.
*COX1↓, Rutin protected intestine from methotrexate, an antimetabolite used in cancer therapy, and induced lesions by inhibiting the expression of COX-1, COX-2, and 15-lipoxygenase
*COX2/PTGS2↓,
*15-LOX/ALOX15↓,
RenoP↑, rutin might protect the kidney from doxorubicin-induced nephrotoxicity, probably by up-regulation of the activity of antioxidant enzymes.
*toxicity↓, According to clinical trials, the safe dosage of rutin is 500 mg/day (Sharma et al. 2013). Rutin is nontoxic both acutely and chronically and no evidence of injury has been found due to rutin administration
| - |
Review, |
Var, |
NA |
|
|
|
- |
Review, |
AD, |
NA |
|
|
|
TumCCA↑, Spermidine specifically interferes with the tumour cell cycle, resulting in the inhibition of tumor cell proliferation and suppression of tumor growth.
TumCP↓,
TumCG↓,
*Inflam↓, health improving effects, that includes remarkable anti-inflammatory effects
*antiOx↑, It is also a potent antioxidant, and reportedly improves the respiratory function
*neuroP↑, Dietary intake of spermidine reduces the risk of neurodegeneration, metabolic diseases, heart ailments, and cancer.
*cognitive↑, spermidine-induced autophagy slows the rate of cognitive decline due to its ability to clear amyloid-beta plaques in the brain
*Aβ↓,
*mitResp↑, Spermidine supplementation also enhances mitochondrial metabolism, and translational activity.
AntiCan↑, anticancer properties of spermidine are of particular interest as it is known to reduce the cancer-related mortality in humans
TumCD↑, in addition to impacting their discourse with the immune effectors that result in expediting the identification of tumor-associated antigens and eventually cancer cell death
TumAuto↑, Inhibition of acetyltransferase EP300 by spermidine is known to induce autophagy, which is one of the desirable approaches in the treatment of cancer.
*AntiAge↑, Lifelong oral spermidine administration is reported to extend the lifespan in mice by 25%, as evidenced by genetic investigations.
LC3B-II↑, Western blotting experiments have showed a surge in the levels of LC3 II/LC3 I, Atg5, and Beclin 1 proteins in spermidine administered HeLa cells.
ATG5↑,
Beclin-1/ATG6↑,
mt-ROS↑, Spermidine induces mitochondrial reactive oxygen species (mtROS) mediated M2-polarization by producing a surge in the levels of H2O2 and mitochondrial peroxide in the presence of spermidine.
H2O2↑,
Apoptosis↑, Spermine is known to induce apoptosis in primary human cells as well as the malignant tumor cells by producing a surge in the intracellular level of reactive oxygen species (ROS)
*ROS↑,
ChemoSen↑, A combination of 5-fluorouracil and spermine analogues N 1 , N 11 -diethylnorspermine (DENSPM) (6, Figure 5) at concentrations 1.25, 2.5, 5, and 10 μM or α-difluoromethylornithine (DFMO) led to a synergistic killing of HCT116 colon carcinoma cells
MMP↓, and loss of membrane potential of mitochondria followed by a subsequent release of cytochrome c
Cyt‑c↑,
*motorD↑, increased positive effects of urolithin A and a combination treatment of urolithin A+EGCG in hAbKI mice for phenotypic behavioral changes including motor coordination, locomotion/exploratory activity, spatial learning and working memory
*memory↑,
*MitoP↑, mitophagy and autophagy genes were upregulated
*Aβ↓, The levels of amyloid beta (Aβ) 40 and Aβ42 are reduced in both treatments, however, the reduction is higher for combined treatment
*mitResp↑, Mitochondrial respiration is stronger for urolithin A compared to EGCG, indicating that mitophagy enhancer, urolithin A is a better and more promising molecule to enhance mitophagy activity.
*Nrf1↑, table4
*PINK1↑,
*PARK2↑,
*ATG5↑,
*Bcl-2↑,
*H2O2↓, we found hydrogen peroxide levels were reduced in urolithin A (p = 0.0008) and urolithin A+EGCG (p = 0.0004) treated hAbKI mice relative to untreated mice.
*ROS↓, urolithin A and EGCG act as free radical scavengers in hAbKI mice
*lipid-P↓, (lipid peroxidation) were also significantly reduced in urolithin A (p = 0.0003) and urolithin A+EGCG (p = 0.0002) treated hAbKI mice relative to untreated hAbKI mice
*mt-ATP↑, mitochondrial ATP levels were increased in urolithin A (p = 0.007) and urolithin A+EGCG (p = 0.0002) treated hAbKI mice relative to hAbKI untreated mice.
Showing Research Papers: 1 to 27 of 27
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 27
Pathway results for Effect on Cancer / Diseased Cells:
NA, unassigned(tgid=0) ⓘ
ATG13↑, 1, ATG16L1↑, 1, EDEM↑, 1, MYCN↓, 1, RUBCN↓, 1, TFE3↑, 1, THEM4/CTMP↑, 1, TNFRSF25/DR3/APO3/LARD/TRAMP/WSL1↑, 1, ULK1/ATG1↑, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↑, 1, Catalase↓, 1, Catalase↑, 1, Ferroptosis↑, 1, GSH↓, 2, H2O2↑, 1, HO-1↓, 1, Iron↑, 2, lipid-P↓, 1, MDA↓, 1, MDA↑, 2, NRF2↑, 2, PARK2↑, 1, ROS↑, 15, mt-ROS↑, 2, SIRT3↑, 1, SOD↑, 2, TrxR1↓, 1,
Metal & Cofactor Biology(tgid=2) ⓘ
FTH1↓, 1, NCOA4↑, 1, TfR1/CD71↓, 1,
Mitochondria & Bioenergetics(tgid=3) ⓘ
ATP↓, 2, CDC2↓, 2, CDC25↓, 2, MEK↓, 1, mitResp↓, 1, MMP↓, 10, MMP↑, 1, mtDam↑, 2, PINK1↑, 1, c-Raf↓, 1, XIAP↓, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
ACSL4↑, 1, AMPK↑, 3, p‑AMPK↑, 1, ATG7↑, 5, BCAP↓, 1, cMyc↓, 1, Glycolysis↓, 1, HK2↓, 1, lactateProd↓, 1, PCK1↓, 1, PDK1 / PDPK1↓, 1,
Cell Death(tgid=5) ⓘ
Akt↓, 7, p‑Akt↓, 3, APAF1↑, 2, Apoptosis↑, 14, mt-Apoptosis↑, 1, BAD↑, 2, Bak↑, 1, BAX↑, 9, Bax:Bcl2↑, 5, Bcl-2↓, 9, Bcl-xL↓, 3, Casp↑, 2, cl‑Casp↑, 1, Casp3↓, 1, Casp3↑, 12, cl‑Casp3↑, 5, proCasp3↓, 1, Casp8↓, 1, Casp8↑, 4, Casp9↑, 7, cl‑Casp9↑, 1, Chk2↑, 1, Cyt‑c↓, 1, Cyt‑c↑, 7, Diablo↑, 1, DR5↑, 3, Fap1↓, 2, Fas↑, 5, FasL↑, 2, Ferroptosis↑, 1, IAP2/BIRC3↓, 1, iNOS↓, 3, JNK↓, 1, JNK↑, 3, MAPK↓, 5, Mcl-1↑, 1, MDM2↓, 1, Myc↓, 1, p38↑, 1, p‑p38↓, 1, survivin↓, 4, TRPV1↑, 1, TumCD↑, 3, YAP/TEAD↓, 1,
Kinase & Signal Transduction(tgid=6) ⓘ
CaMKII
↓, 1, EF-1α↓, 1, Sp1/3/4↓, 1, TSC2↑, 1,
Transcription & Epigenetics(tgid=7) ⓘ
cJun↑, 2, H3↑, 1, p‑H3↓, 1, H4↑, 1, HATs↑, 1, other↓, 1, tumCV↓, 4,
Protein Folding & ER Stress(tgid=8) ⓘ
CHOP/DDIT3↓, 1, CHOP/DDIT3↑, 4, cl‑CHOP/DDIT3↑, 1, eIF2α↓, 1, eIF2α↑, 1, ER Stress↑, 7, GRP78/BiP↑, 4, HSP27↓, 2, HSP90↑, 1, IRE1↑, 1, PERK↑, 1, UPR↑, 2, XBP-1↑, 1,
Autophagy & Lysosomes(tgid=9) ⓘ
ATG3↑, 4, ATG5↑, 25, Beclin-1/ATG6↑, 19, LC3‑Ⅱ/LC3‑Ⅰ↑, 4, LC3B↑, 1, LC3B-II↑, 3, LC3I↓, 1, LC3I↑, 1, LC3II↑, 10, LC3s↑, 1, MitoP↑, 1, p62↓, 4, p62↑, 4, TumAuto↑, 16,
DNA Damage & Repair(tgid=10) ⓘ
ATM↑, 1, CHK1↑, 1, DNAdam↑, 2, DNMT1↓, 1, GADD45A↑, 1, P53↑, 6, PARP↑, 3, cl‑PARP↑, 9, PCNA↓, 3, TP53↓, 1,
Cell Cycle & Senescence(tgid=11) ⓘ
CDK1↑, 1, CDK2↓, 2, CDK4↓, 2, CycB/CCNB1↓, 2, cycD1/CCND1↓, 2, P21?, 1, P21↑, 2, p‑RB1↓, 1, TumCCA↑, 10,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
4E-BP1↓, 1, CD133↓, 1, CD44↓, 1, cMET↓, 1, p‑cMET↑, 1, CSCs↓, 2, EMT↓, 2, ERK↓, 4, p‑ERK↑, 1, GSK‐3β↑, 2, HDAC↓, 1, IGF-1R↑, 1, mTOR↓, 6, p‑mTOR↓, 3, mTORC1↓, 2, mTORC2↓, 1, Nanog↓, 1, Nestin↓, 1, NOTCH1↓, 1, NOTCH3↓, 2, OCT4↓, 1, P70S6K↓, 1, PI3K↓, 8, PTEN↑, 1, RAS↓, 1, SOX2↓, 1, STAT3↓, 3, STAT3↝, 1, TumCG↓, 6, Wnt↓, 3, Wnt↑, 1,
Migration(tgid=13) ⓘ
AP-1↓, 1, Ca+2↓, 1, Ca+2↑, 5, i-Ca+2?, 1, CCN2/CTGF↓, 1, CD31/PECAM-1↓, 1, Chl↑, 1, E-cadherin↑, 1, Ki-67↓, 1, miR-486↑, 1, MMP-10↓, 1, MMP13↓, 1, MMP2↓, 1, MMP3↓, 1, MMP7↓, 1, MMP9↓, 2, MMPs↓, 3, PAK1↓, 1, PKCδ↓, 1, RAGE↓, 1, Rho↓, 1, SOX4↓, 1, TIMP2↑, 1, TSC1↑, 1, TumCI↓, 2, TumCMig↓, 2, TumCP↓, 10, TumMeta↓, 2, uPA↓, 2, Zeb1↓, 1, Zeb1↑, 1, β-catenin/ZEB1↓, 3, β-catenin/ZEB1↑, 1,
Angiogenesis & Vasculature(tgid=14) ⓘ
angioG↓, 4, ATF4↑, 3, EGFR↓, 1, Endoglin↑, 1, Hif1a↓, 2, VEGF↓, 5, VEGFR2/KDR/Flk1↓, 3,
Barriers & Transport(tgid=15) ⓘ
BBB∅, 1, GLUT1↓, 1, P-gp/ABCB1↓, 3,
Immune & Inflammatory Signaling(tgid=16) ⓘ
COX2/PTGS2↓, 3, IFN-γ↓, 1, IKKα↓, 1, IL1β↓, 1, IL2↓, 1, IL4↓, 1, Imm↑, 2, JAK1↓, 1, NF-kB↓, 5, p65↓, 1, PD-L1↓, 1, PGE2↓, 1, TNF-α↓, 2, TNF-α↑, 2,
Protein Aggregation(tgid=19) ⓘ
PP2A↑, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
ABCG2↓, 2, BioAv↓, 1, BioEnh↑, 1, ChemoSen↑, 6, Dose↝, 3, eff↓, 5, eff↑, 7, Half-Life↓, 2, Half-Life↝, 1, MDR1↓, 1, MRP1/ABCC1↓, 1, RadioS↑, 2, selectivity↑, 6,
Clinical Biomarkers(tgid=22) ⓘ
EGFR↓, 1, Ki-67↓, 1, Myc↓, 1, PD-L1↓, 1, RAGE↓, 1, TP53↓, 1,
Functional Outcomes(tgid=23) ⓘ
AntiCan↑, 2, chemoP↑, 1, chemoPv↑, 4, hepatoP↑, 1, neuroP↑, 1, OS↑, 1, PRAS40↑, 1, RenoP↑, 2, Risk↓, 1, toxicity↝, 1, TumVol↓, 2, TumW↓, 2,
Total Targets: 273
Pathway results for Effect on Normal Cells:
NA, unassigned(tgid=0) ⓘ
15-LOX/ALOX15↓, 1, AntiP↑, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↓, 1, antiOx↑, 4, H2O2↓, 1, lipid-P↓, 1, MDA↓, 2, MPO↓, 1, Nrf1↑, 1, PARK2↑, 1, ROS↓, 5, ROS↑, 1, TAC↑, 1,
Mitochondria & Bioenergetics(tgid=3) ⓘ
mt-ATP↑, 1, mitResp↑, 2, MMP∅, 1, PINK1↑, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
glucose↓, 1, LDL↓, 1,
Cell Death(tgid=5) ⓘ
BAX↓, 1, Bcl-2↑, 1, Casp3↓, 1, Casp3∅, 1, Casp9↓, 1, Cyt‑c↓, 1, Cyt‑c∅, 1, JNK↓, 1, MAPK↓, 1, p38↓, 1,
Autophagy & Lysosomes(tgid=9) ⓘ
ATG5↑, 2, Beclin-1/ATG6↑, 1, LC3B↑, 1, MitoP↑, 1,
DNA Damage & Repair(tgid=10) ⓘ
P53↓, 1,
Migration(tgid=13) ⓘ
APP↓, 1, Ca+2?, 1, LRP1↑, 1,
Barriers & Transport(tgid=15) ⓘ
BBB↑, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
COX1↓, 1, COX2/PTGS2↓, 2, IL10↑, 1, IL1β↓, 1, IL4↑, 1, IL6↓, 1, Inflam↓, 8, NF-kB↓, 2, TNF-α↓, 2,
Synaptic & Neurotransmission(tgid=18) ⓘ
tau↓, 1,
Protein Aggregation(tgid=19) ⓘ
Aβ↓, 3, BACE/β-secretase↓, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 4, BioAv↝, 1, Dose↝, 1, eff↑, 1,
Clinical Biomarkers(tgid=22) ⓘ
GutMicro↑, 1, IL6↓, 1,
Functional Outcomes(tgid=23) ⓘ
AntiAge↑, 1, AntiDiabetic↑, 1, cardioP↑, 1, chemoP↑, 1, chemoPv↑, 1, cognitive↑, 2, hepatoP↑, 1, memory↑, 2, motorD↑, 1, neuroP↑, 3, Pain↓, 1, radioP↑, 1, toxicity↓, 2, toxicity↑, 1, Wound Healing↑, 1,
Infection & Microbiome(tgid=24) ⓘ
AntiViral↑, 1, Bacteria↓, 1, Diar↓, 1,
Total Targets: 74
Scientific Paper Hit Count for: ATG5, Autophagy-related 5
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#:723 State#:% Dir#:2
wNotes=on sortOrder:rid,rpid
Home Page