ATG5 Cancer Research Results
ATG5, Autophagy-related 5: Click to Expand ⟱
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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).
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Scientific Papers found: Click to Expand⟱
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vitro+vivo, |
ESCC, |
TE1 |
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vitro+vivo, |
ESCC, |
KYSE-510 |
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in-vitro, |
Nor, |
Het-1A |
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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
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↑,
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↑,
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↓, 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↑,
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↓, 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
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in-vitro, |
Pca, |
PC3 |
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in-vivo, |
PC, |
NA |
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in-vitro, |
Pca, |
LNCaP |
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in-vitro, |
Pca, |
WPMY-1 |
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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↑,
TumAuto↑, citrate induces autophagy of prostate cancer cells
CaMKII
↓, citrate suppresses the activation of the CaMKI
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in-vitro, |
GC, |
SGC-7901 |
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in-vitro, |
GC, |
BGC-823 |
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TumCP↓,
Apoptosis↑,
TumAuto↑,
P53↑,
PI3K↓,
P21↑,
p‑Akt↓,
p‑mTOR↓,
Bcl-2↓,
Bcl-xL↓,
LC3I↓, LC3I
BAX↑,
Beclin-1↑,
cl‑Casp3↑,
cl‑PARP↑,
LC3II↑,
ATG3↑,
ATG5↑,
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Review, |
Var, |
NA |
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Review, |
AD, |
NA |
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Beclin-1↑, 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↑, 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↑,
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↓, Fisetin inhibited the VEGFR expression in Y79 cells as well as the angiogenesis of a tumor.
IAP2↓, 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
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in-vitro, |
OS, |
U2OS |
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in-vivo, |
NA, |
NA |
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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
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↓,
*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↓,
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↑, ↑ 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↓, 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.
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in-vivo, |
Lung, |
A549 |
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in-vitro, |
Lung, |
A549 |
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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↑,
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↑,
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↓,
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Review, |
Var, |
NA |
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Review, |
AD, |
NA |
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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↑,
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 16 of 16
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 16
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 1, Catalase↓, 1, Ferroptosis↑, 1, GSH↓, 1, H2O2↑, 1, HO-1↓, 1, Iron↑, 2, lipid-P↓, 1, MDA↓, 1, MDA↑, 1, NRF2↑, 2, ROS↑, 10, mt-ROS↑, 2, SIRT3↑, 1, SOD↑, 1,
Metal & Cofactor Biology ⓘ
FTH1↓, 1, NCOA4↑, 1, TfR1/CD71↓, 1,
Mitochondria & Bioenergetics ⓘ
CDC2↓, 1, CDC25↓, 1, MEK↓, 1, MMP↓, 7, MMP↑, 1, c-Raf↓, 1, XIAP↓, 1,
Core Metabolism/Glycolysis ⓘ
ACSL4↑, 1, AMPK↑, 1, p‑AMPK↑, 1, ATG7↑, 3, BCAP↓, 1, cMyc↓, 1, lactateProd↓, 1, PCK1↓, 1,
Cell Death ⓘ
Akt↓, 3, p‑Akt↓, 2, APAF1↑, 1, Apoptosis↑, 9, BAD↑, 1, Bak↑, 1, BAX↑, 3, Bax:Bcl2↑, 2, Bcl-2↓, 4, Bcl-xL↓, 2, Casp↑, 1, Casp3↓, 1, Casp3↑, 8, cl‑Casp3↑, 2, Casp8↓, 1, Casp8↑, 2, Casp9↑, 5, Chk2↑, 1, Cyt‑c↓, 1, Cyt‑c↑, 3, Diablo↑, 1, DR5↑, 2, Fap1↓, 2, Fas↑, 2, Ferroptosis↑, 1, IAP2↓, 1, iNOS↓, 2, JNK↓, 1, JNK↑, 2, MAPK↓, 3, Mcl-1↑, 1, Myc↓, 1, p‑p38↓, 1, survivin↓, 3, TRPV1↑, 1, TumCD↑, 2,
Kinase & Signal Transduction ⓘ
CaMKII
↓, 1, EF-1α↓, 1,
Transcription & Epigenetics ⓘ
cJun↑, 1, H3↑, 1, p‑H3↓, 1, H4↑, 1, HATs↑, 1, other↓, 1, tumCV↓, 2,
Protein Folding & ER Stress ⓘ
CHOP↑, 1, cl‑CHOP↑, 1, ER Stress↑, 3, GRP78/BiP↑, 3, HSP27↓, 1, UPR↑, 1,
Autophagy & Lysosomes ⓘ
ATG3↑, 2, ATG5↑, 15, Beclin-1↑, 10, LC3‑Ⅱ/LC3‑Ⅰ↑, 3, LC3B↑, 1, LC3B-II↑, 2, LC3I↓, 1, LC3I↑, 1, LC3II↑, 5, LC3s↑, 1, p62↓, 3, p62↑, 3, TumAuto↑, 8,
DNA Damage & Repair ⓘ
ATM↑, 1, CHK1↑, 1, DNAdam↑, 2, P53↑, 4, PARP↑, 2, cl‑PARP↑, 5, PCNA↓, 2, TP53↓, 1,
Cell Cycle & Senescence ⓘ
CDK2↓, 2, CDK4↓, 2, cycD1/CCND1↓, 2, P21?, 1, P21↑, 1, p‑RB1↓, 1, TumCCA↑, 5,
Proliferation, Differentiation & Cell State ⓘ
CD133↓, 1, CD44↓, 1, CSCs↓, 1, EMT↓, 1, ERK↓, 2, p‑ERK↑, 1, GSK‐3β↑, 1, HDAC↓, 1, IGF-1R↑, 1, mTOR↓, 4, p‑mTOR↓, 1, mTORC1↓, 2, mTORC2↓, 1, Nanog↓, 1, Nestin↓, 1, NOTCH1↓, 1, NOTCH3↓, 2, OCT4↓, 1, PI3K↓, 5, PTEN↑, 1, RAS↓, 1, SOX2↓, 1, STAT3↓, 2, TumCG↓, 4, Wnt↑, 1,
Migration ⓘ
Ca+2↓, 1, Ca+2↑, 4, i-Ca+2?, 1, E-cadherin↑, 1, Ki-67↓, 1, miR-486↑, 1, MMP13↓, 1, MMP7↓, 1, MMP9↓, 1, MMPs↓, 2, Rho↓, 1, SOX4↓, 1, TumCI↓, 1, TumCMig↓, 1, TumCP↓, 6, TumMeta↓, 1, uPA↓, 1, Zeb1↓, 1, Zeb1↑, 1, β-catenin/ZEB1↓, 1, β-catenin/ZEB1↑, 1,
Angiogenesis & Vasculature ⓘ
angioG↓, 1, ATF4↑, 1, Endoglin↑, 1, Hif1a↓, 1, VEGF↓, 2, VEGFR2↓, 2,
Barriers & Transport ⓘ
P-gp↓, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 2, IFN-γ↓, 1, IKKα↓, 1, IL2↓, 1, IL4↓, 1, Imm↑, 1, JAK1↓, 1, NF-kB↓, 3, p65↓, 1, PGE2↓, 1, TNF-α↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 1, ChemoSen↑, 4, Dose↝, 3, eff↓, 2, eff↑, 5, Half-Life↓, 2, Half-Life↝, 1, RadioS↑, 1, selectivity↑, 5,
Clinical Biomarkers ⓘ
Ki-67↓, 1, Myc↓, 1, TP53↓, 1,
Functional Outcomes ⓘ
AntiCan↑, 2, chemoP↑, 1, chemoPv↑, 1, hepatoP↑, 1, neuroP↑, 1, OS↑, 1, RenoP↑, 1, TumVol↓, 2, TumW↓, 2,
Total Targets: 197
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 4, H2O2↓, 1, lipid-P↓, 1, MPO↓, 1, Nrf1↑, 1, PARK2↑, 1, ROS↓, 4, ROS↑, 1,
Mitochondria & Bioenergetics ⓘ
mt-ATP↑, 1, mitResp↑, 2, MMP∅, 1, PINK1↑, 1,
Core Metabolism/Glycolysis ⓘ
glucose↓, 1, LDL↓, 1,
Cell Death ⓘ
BAX↓, 1, Bcl-2↑, 1, Casp3∅, 1, Cyt‑c↓, 1, Cyt‑c∅, 1,
Autophagy & Lysosomes ⓘ
ATG5↑, 1, MitoP↑, 1,
Migration ⓘ
Ca+2?, 1,
Barriers & Transport ⓘ
BBB↑, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 1, Inflam↓, 6, NF-kB↓, 2,
Protein Aggregation ⓘ
Aβ↓, 2,
Drug Metabolism & Resistance ⓘ
eff↑, 1,
Functional Outcomes ⓘ
AntiAge↑, 1, cardioP↑, 1, cognitive↑, 1, memory↑, 2, motorD↑, 1, neuroP↑, 3, Pain↓, 1, toxicity↓, 1, Wound Healing↑, 1,
Infection & Microbiome ⓘ
Bacteria↓, 1, Diar↓, 1,
Total Targets: 39
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
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