p62 Cancer Research Results

p62, p62/sequestosome 1 (SQSTM1): Click to Expand ⟱

Source:

Type:

A protein that plays a crucial role in various cellular processes, including autophagy, cell signaling, and protein degradation.
p62 is a scaffold protein that interacts with various signaling molecules, including kinases, phosphatases, and ubiquitin ligases. It is also a substrate of autophagy, a process by which cells recycle damaged or dysfunctional organelles and proteins.
p62 is overexpressed in various types of cancer, including breast, lung, colon, and liver cancer.
Its overexpression has been associated with poor prognosis and reduced survival in some cancers.

Scientific Papers found: Click to Expand⟱

5237-

AgNPs,

Nrf2 Activation Mitigates Silver Nanoparticle-Induced Ferroptosis in Hepatocytes

in-vitro,

Liver,

HepG2

Ferroptosis↑, we provide evidence that AgNPs trigger ferroptosis in both mouse hepatocytes and HepG2 cells
p62↑, AgNPs increased p62 expression, which in turn stabilized Nrf2 by suppressing its interaction with Keap1.
NRF2↝,
eff↓, Upon activation, Nrf2 enhances the transcription of key antioxidant enzymes, including NQO1 and HO-1, thereby alleviating ferroptosis.

317-

AgNPs,

Autophagic effects and mechanisms of silver nanoparticles in renal cells under low dose exposure

in-vitro,

Kidney,

HEK293

TumAuto↑,
p62↑, P62 was elevated in AgNPs-treated cells in an mTOR-independent manner.

357-

AgNPs,

Hypoxia-mediated autophagic flux inhibits silver nanoparticle-triggered apoptosis in human lung cancer cells

in-vitro,

Lung,

A549

in-vitro,

Lung,

L132

mtDam↑,
ROS↑,
Hif1a↑, HIF-1α expression was upregulated after AgNPs treatment under both hypoxic and normoxic conditions HIF-1α knockdown enhances hypoxia induced decrease in cell viability
LC3s↑,
p62↑,
eff↓, Hypoxia decreases the effects of anticancer drugs in solid tumor cells through the regulation of HIF-1α

2287-

AgNPs,

Silver nanoparticles induce endothelial cytotoxicity through ROS-mediated mitochondria-lysosome damage and autophagy perturbation: The protective role of N-acetylcysteine

in-vitro,

Nor,

HUVECs

*TumCP↓, AgNPs affects the morphology and function of endothelial cells which manifests as decreased cell proliferation, migration, and angiogenesis ability
*ROS↑, AgNPs can induce excessive cellular production of reactive oxygen species (ROS), leading to damage to cellular sub-organs such as mitochondria and lysosomes
*eff↓, treatment with ROS scavenger-NAC can effectively suppress AgNP-induced endothelial damage.
*MDA↑, exposure to AgNPs increased MDA levels and decreased GSH levels.
*GSH↓,
*MMP↓, significantly reduced both MMP and ATP levels (Fig. 7) in HUVECs,
*ATP↓,
*LC3II↑, expression levels of LC3-II and p62 were significantly increase
*p62↑,
*Bcl-2↓, the anti-apoptotic protein expression level of Bcl-2 in HUVECs decreased, while the pro-apoptotic protein expression levels of Bax and Caspase-3 increased significantly.
*BAX↑,
*Casp3↑,

265-

ALA,

Alpha-Lipoic Acid Reduces Cell Growth, Inhibits Autophagy, and Counteracts Prostate Cancer Cell Migration and Invasion: Evidence from In Vitro Studies

in-vitro,

Pca,

LNCaP

 ALA (25–1000 μM) for 48 h

in-vitro,

Pca,

DU145

ROS↓, ALA decreased ROS production, SOD1 and GSTP1 protein expression
SOD↓, SOD1, DU145
GSTP1/GSTπ↓,
NRF2↓, significantly reduced the cytosolic and nuclear content of the transcription factor Nrf2
p62↓, du145
p62↑, LNCaP
SOD↑, LNCaP
p‑mTOR↑, revealed that in both cancer cells, ALA, by upregulating pmTOR expression, reduced the protein content of two autophagy initiation markers, Beclin-1 and MAPLC3.
Beclin-1↓,
ROS↑, Interestingly, in LNCaP cells, we observed an almost significant increase in ROS content (p = 0.06) after ALA compared to the control, concomitantly with a significant upregulation of the antioxidant enzyme SOD1 after 48 h.
SOD1↑,

1563-

Api,

MET,

Metformin-induced ROS upregulation as amplified by apigenin causes profound anticancer activity while sparing normal cells

in-vitro,

Nor,

HDFa

metformin (5 mM), apigenin (1 or 20 µM),

in-vitro,

PC,

AsPC-1

in-vitro,

PC,

MIA PaCa-2

in-vitro,

Pca,

DU145

in-vitro,

Pca,

LNCaP

in-vivo,

NA,

mice

selectivity↑, Metformin increased cellular ROS levels in AsPC-1 pancreatic cancer cells, with minimal effect in HDF, human primary dermal fibroblasts.
selectivity↑, Metformin reduced cellular ATP levels in HDF, but not in AsPC-1 cells
selectivity↓, Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells
ROS↑,
eff↑, Metformin combined with apigenin increased ROS levels dramatically and decreased cell viability in various cancer cells including AsPC-1 cells, with each drug used singly having a minimal effect.
tumCV↓,
MMP↓, Metformin/apigenin combination synergistically decreased mitochondrial membrane potential in AsPC-1 cells but to a lesser extent in HDF cells
Dose∅, co-treatment with metformin (0.05, 0.5 or 5 mM) and apigenin (20 µM) dramatically increased cellular ROS levels in AsPC-1 cells
eff↓, NAC blocked the metformin/apigenin co-treatment-induced cell death in AsPC-1 cells
DNAdam↑, Combination of metformin and apigenin leads to DNA damage-induced apoptosis, autophagy and necroptosis in AsPC-1 cells but not in HDF cells
Apoptosis↑,
TumAuto↑,
Necroptosis↑,
p‑P53↑, p-p53, Bim, Bid, Bax, cleaved PARP, caspase 3, caspase 8, and caspase 9 were also significantly increased by combination of metformin and apigenin in AsPC-1
BIM↑,
BAX↑,
p‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
Cyt‑c↑, Cytochrome C was also released from mitochondria in AsPC-1 cell
Bcl-2↓,
AIF↑, Interestingly, autophagy-related proteins (AIF, P62 and LC3B) and necroptosis-related proteins (MLKL, p-MLKL, RIP3 and p-RIP3) were also increased by combination of metformin and apigenin
p62↑,
LC3B↑,
MLKL↑,
p‑MLKL↓,
RIP3↑,
p‑RIP3↑,
TumCG↑, in vivo
TumW↓, metformin (125 mg/kg) or apigenin (40 mg/kg) caused a reduction of tumor size compared to the control group (Fig. 7D). However, oral administration of combination of metformin and apigenin decreased tumor weight profoundly

1377-

BBR,

Berberine inhibits autophagy and promotes apoptosis of fibroblast-like synovial cells from rheumatoid arthritis patients through the ROS/mTOR signaling pathway

in-vitro,

Arthritis,

10, 20, 30, 40, 50, 60, 70, and 80 μmol/L berberine

Apoptosis↑, 30 μmol/L
MMP↓,
Bax:Bcl2↑,
LC3‑Ⅱ/LC3‑Ⅰ↓, Berberine treatment obviously decreased the ratios of Bcl-2/Bax (P < 0.05) and LC3B-II/I (P < 0.01)
p62↑,
*ROS↓,

5634-

BCA,

Molecular Mechanisms of Biochanin A in AML Cells: Apoptosis Induction and Pathway-Specific Regulation in U937 and THP-1

in-vitro,

AML,

U937

in-vitro,

AML,

THP1

Apoptosis↑, Biochanin A induced dose-dependent apoptosis, as evidenced by caspase-7 activation and PARP1 cleavage.
Casp7↑,
PARP1↑,
Bcl-2↓, Biochanin A downregulated oncogenes such as RUNX1, BCL2, and MYC while upregulating CHOP (GADD153), CDKN1A (p21), and SQSTM1 (p62), contributing to apoptosis and cell cycle arrest across both cell lines.
Myc↓,
CHOP↑,
P21↑,
p62↑,
TumCCA↑,
TXNIP↑, In contrast, in U937 cells, Biochanin A upregulated TXNIP and downregulated CCND2, highlighting the involvement of oxidative stress and G1/S cell cycle arrest.
ROS↑,
*antiOx↑, Biochanin A exhibits a broad spectrum of biological activities, including antioxidant, anti-inflammatory, estrogenic, metabolic regulatory, neuroprotective, and anticancer effects [1].
*Inflam↓,
*neuroP↑,
AntiCan↑,
TumCP↓, The anticancer mechanisms of Biochanin A involve the inhibition of cell proliferation via the modulation of cyclins and cyclin-dependent kinases
angioG↓, inhibition of angiogenesis and metastasis through downregulation of VEGF and matrix metalloproteinases (MMPs), and activation of apoptosis
TumMeta↓,
VEGF↓,
MMPs↓,
tumCV↓, Biochanin A significantly inhibited cell viability at concentrations ≥100 μM in U937 cells and ≥50 μM in THP-1 cells
DNAdam↑, Biochanin A induces a DNA damage response
CHOP↑, In our study, we observed a significant induction of CHOP protein expression following treatment with Biochanin A at concentrations of 100 μM and 200 μM.
cMyc↓, Biochanin A inhibited c-Myc protein expression in U937 and THP-1 cells
BioAv↓, Biochanin A remains limited due to its poor aqueous solubility and rapid systemic clearance, which render the 100–200 μM concentrations used in this study difficult to achieve in vivo
Half-Life↓,
BioAv↑, PEG-NLC formulations have been shown to significantly increase the plasma half-life and bioavailability of flavonoids

2720-

BetA,

Betulinic acid induces apoptosis of HeLa cells via ROS-dependent ER stress and autophagy in vitro and in vivo

in-vitro,

Cerv,

HeLa

Keap1↝, The findings revealed that BA activated Keap1/Nrf2 pathway and triggered mitochondria-dependent apoptosis due to ROS production.
ROS↑,
Ca+2↑, Furthermore, BA increased the intracellular Ca2+ levels
Beclin-1↓, inhibited the expression of Beclin1 and promoted the expression of GRP78, LC3-II, and p62 associated with ERS and autophagy.
GRP78/BiP↑,
LC3II↑,
p62↑,
ERStress↑,
TumAuto↑,

5678-

BML,

Bromelain inhibits the ability of colorectal cancer cells to proliferate via activation of ROS production and autophagy

in-vivo,

CRC,

investigated using different CRC cell lines, a zebrafish model, and a xenograft mouse model.

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.

1101-

CA,

Tras,

Cooperative antitumor activities of carnosic acid and Trastuzumab in ERBB2+ breast cancer cells

in-vitro,

BC,

 in ERBB2+ BC cells

ChemoSen↑, CA reversibly enhances Tz inhibition of cell survival, cooperatively inhibits cell migration and induces cell cycle arrest in G0/G1
HER2/EBBR2↓,
PI3K↓,
Akt↓,
mTOR↓,
p62↑,

2019-

CAP,

Capsaicin: A Two-Decade Systematic Review of Global Research Output and Recent Advances Against Human Cancer

Review,

Var,

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

872-

CUR,

RES,

New Insights into Curcumin- and Resveratrol-Mediated Anti-Cancer Effects

in-vitro,

BC,

TUBO

15uM, 15uM

in-vitro,

BC,

SALTO

TumCP↓,
tumCV↓,
p62↓, reduced by Cur
p62↑, accumulated by Res
TumAuto↑, Cur only
TumAuto↓, Res only
ROS↑, increased ROS with Res
ROS↓, decreased ROS with Cur or combination
CHOP↑, strongly upregulated by the curcumin/resveratrol combination

477-

CUR,

Curcumin induces G2/M arrest and triggers autophagy, ROS generation and cell senescence in cervical cancer cells

in-vitro,

Cerv,

SiHa

5, 15, 30 and 50 µM, 6, 12, 24 and 48 h

TumCP↓,
TumCCA↑, Inducing G2/M cell cycle arrest
Apoptosis↑,
TumAuto↑,
CycB/CCNB1↓, cyclins B1
CDC25↓,
ROS↑,
p62↑,
LC3‑Ⅱ/LC3‑Ⅰ↑,
cl‑Casp3↑,
cl‑PARP↑,
P53↑,
P21↑,

448-

CUR,

Heat shock protein 27 influences the anti-cancer effect of curcumin in colon cancer cells through ROS production and autophagy activation

in-vitro,

CRC,

HT-29

15, 20 and 25 μM, 48 h

Apoptosis↑,
TumCCA↑, G2/M cell cycle arrest
p‑Akt↓,
Akt↓,
Bcl-2↓,
p‑BAD↓,
BAD↑,
cl‑PARP↑,
ROS↑,
HSP27↑,
Beclin-1↑,
p62↑,
GPx1↓,
GPx4↓,

4901-

DCA,

Sal,

Dichloroacetate and Salinomycin as Therapeutic Agents in Cancer

Review,

NSCLC,

Glycolysis↓, DCA redirects mitochondrial metabolism away from glycolysis to OXPHOS by the inhibition of PDKs
OXPHOS↑,
PDKs↓,
ROS↑, DCA increases reactive oxygen species (ROS), which induce downstream changes in mitochondrial function, causing the selective apoptosis of cancer cells.
Apoptosis↑,
GlucoseCon↓, treatment with DCA decreased glucose consumption and lactate production in vitro in a manner that was statistically significant compared to the controls
lactateProd↓,
RadioS↑, it enhanced the sensitivity of A549 and H1299 cells to X-ray-induced cell killing
TumAuto↑, DCA has been shown to induce autophagy instead of inhibiting it.
mTOR↓, The DCA-induced induction of autophagy was found to be mediated by the generation of ROS, the inhibition of the mammalian targets of rapamycin (mTOR),
LC3s↓, Lu and colleagues found that LC3 decreased while p62 levels increased, both of which are hallmarks of autophagy inhibition
p62↑,
TumCG↓, In vivo studies have demonstrated that DCA inhibits the growth of A549 and H1975 tumor xenografts and enhances the survival of tumor-bearing nude mice
OS↑,
toxicity↝, the most clinically limiting side effect of DCA is peripheral neuropathy
ChemoSen↑, DCA exerts synergistic potential with the most widely used chemotherapy agent, paclitaxel, on NSCLC cells.
eff↑, DCA has also been shown to have anticancer synergies with various non-traditional agents, the most prominent of which is metformin.
eff↑, Another compound that DCA has been shown to have a strong synergism with is ivermectin.
Ferritin↓, SAL and its derivatives prevent the movement of iron from the lumen to the cytosol, triggering an iron-depletion reaction that is characterized by the rapid degradation of ferritin
CSCs↓, SAL has been shown to selectively target CSCs in vitro and in vivo, but its mode of action is not fully understood.
EMT↓, SAL has also been shown to suppress the epithelial–mesenchymal transition (EMT) as well as transforming growth factors (TGFs). EMT is a process that is pivotal to metastasis.
ROS↑, SAL triggers apoptosis by elevating intracellular ROS levels, leading to the translocation of Bax protein to the mitochondria, cytochrome c (Cytc) release, and the activation of caspase-3
Cyt‑c↑,
Casp3↑,
ER Stress↑, SAL was observed to upregulate ER stress-related proteins in a time-/dose-dependent manner
selectivity↑, SAL induced cell death in multiple apoptosis-resistant cancer cell lines, but not in normal healthy human cells
eff↑, Skeberdytė and colleagues were among the first to recognize that DCA had synergistic potential with SAL.
TumCG↓, DCA and SAL were found to significantly suppress tumor growth in vivo in the mice.

1863-

dietFMD,

Chemo,

Effect of fasting on cancer: A narrative review of scientific evidence

Review,

Var,

eff↑, recommend combining prolonged periodic fasting with a standard conventional therapeutic approach to promote cancer‐free survival, treatment efficacy, and reduce side effects in cancer patients.
ChemoSideEff↓, lowered levels of IGF1 and insulin have the potential to protect healthy cells from side effects
ChemoSen↑,
Insulin↓, causes insulin levels to drop and glucagon levels to rise
HDAC↓, Histone deacetylases are inhibited by ketone bodies, which may slow tumor development.
IGF-1↓, FGF21 rises during intermittent fasting, and it plays a vital role in lowering IGF1 levels by inhibiting phosphorylated STAT5 in the liver
STAT5↓,
BG↓, Fasting suppresses glucose, IGF1, insulin, the MAPK pathway, and heme oxygenase 1
MAPK↓,
HO-1↓,
ATG3↑, while increasing many autophagy‐regulating components (Atgs, LC3, Beclin1, p62, Sirt1, and LAMP2).
Beclin-1↑,
p62↑,
SIRT1↑,
LAMP2↑,
OXPHOS↑, Fasting causes cancer cells to release oxidative phosphorylation (OXPHOS) through aerobic glycolysis
ROS↑, which leads to an increase in reactive oxygen species (ROS), p53 activation, DNA damage, and cell death in response to chemotherapy.
P53↑,
DNAdam↑,
TumCD↑,
ATP↑, and causes extracellular ATP accumulation, which inhibits Treg cells and the M2 phenotype while activating CD8+ cytotoxic T cells.
Treg lymp↓,
M2 MC↓,
CD8+↑,
Glycolysis↓, By lowering glucose intake and boosting fatty acid oxidation, fasting can induce a transition from aerobic glycolysis to mitochondrial oxidative phosphorylation in cancerous cells, resulting in increased ROS
GutMicro↑, Fasting has been shown to have a direct impact on the gut microbial community's constitution, function, and interaction with the host, which is the complex and diverse microbial population that lives in the intestine
GutMicro↑, Fasting also reduces the number of potentially harmful Proteobacteria while boosting the levels of Akkermansia muciniphila.
Warburg↓, Fasting generates an anti‐Warburg effect in colon cancer models, which increases oxygen demand but decreases ATP production, indicating an increase in mitochondrial uncoupling.
Dose↝, Those patients fasted for 36 h before treatment and 24 h thereafter, having a total of 350 calories per day. Within 8 days of chemotherapy, no substantial weight loss was recorded, although there was an improvement in quality of life and weariness.

5008-

DSF,

Cu,

Overcoming the compensatory elevation of NRF2 renders hepatocellular carcinoma cells more vulnerable to disulfiram/copper-induced ferroptosis

in-vitro,

HCC,

selectivity↑, We found that DSF/Cu selectively exerted an efficient cytotoxic effect on HCC cell lines, and potently inhibited migration, invasion, and angiogenesis of HCC cells
TumCD↑,
TumCMig↓,
TumCI↓,
angioG↓,
mtDam↑, Importantly, we confirmed that DSF/Cu could intensively impair mitochondrial homeostasis, increase free iron pool, enhance lipid peroxidation, and eventually result in ferroptotic cell death.
Iron↑,
lipid-P↑,
Ferroptosis↑,
NF-kB↑, Of note, a compensatory elevation of NRF2 accompanies the process of ferroptosis, and contributes to the resistance to DSF/Cu.
p‑p62↑, DSF/Cu dramatically activated the phosphorylation of p62, which facilitates competitive binding of Keap1, thus prolonging the half-life of NRF2.
Keap1↓,
eff↑, inhibition of NRF2 expression via RNA interference or pharmacological inhibitors significantly facilitated the accumulation of lipid peroxidation, and rendered HCC cells more sensitive to DSF/Cu induced ferroptosis
eff↓, Conversely, fostering NRF2 expression was capable of ameliorating the cell death activated by DSF/Cu.
ChemoSen↑, Additionally, DSF/Cu could strengthen the cytotoxicity of sorafenib, and arrest tumor growth both in vitro and in vivo, by simultaneously inhibiting the signal pathway of NRF2 and MAPK kinase.

1654-

FA,

Molecular mechanism of ferulic acid and its derivatives in tumor progression

Review,

Var,

AntiCan↑, FA has anti-inflammatory, analgesic, anti-radiation, and immune-enhancing effects and also shows anticancer activity,
Inflam↓,
RadioS↑,
ROS↑, FA can cause mitochondrial apoptosis by inducing the generation of intracellular reactive oxygen species (ROS)
Apoptosis↑,
TumCCA↑, G0/G1 phase
TumCMig↑, inducing autophagy; inhibiting cell migration, invasion, and angiogenesis
TumCI↓,
angioG↓,
ChemoSen↑, synergistically improving the efficacy of chemotherapy drugs and reducing adverse reactions.
ChemoSideEff↓,
P53↑, FA could increase the expression level of p53 in MIA PaCa-2 pancreatic cancer cells
cycD1/CCND1↓, while reducing the expression levels of cyclin D1 and cyclin-dependent kinase (CDK) 4/6.
CDK4↓,
CDK6↓,
TumW↓, FA treatment was found to reduce tumor weight in a dose-dependent manner, increase miR-34a expression, downregulate Bcl-2 protein expression, and upregulate caspase-3 protein expression
miR-34a↑,
Bcl-2↓,
Casp3↑,
BAX↑,
β-catenin/ZEB1↓, isoferulic acid dose-dependently downregulated the expression of β-catenin and MYC proto-oncogene (c-Myc), inducing apoptosis
cMyc↓,
Bax:Bcl2↑, FXS-3 can inhibit the activity of A549 cells by upregulating the Bax/Bcl-2 ratio
SOD↓, After treatment with FA, Cao et al. [40] observed an increase in ROS production and a decrease in superoxide dismutase activity and glutathione content in EC-1 and TE-4 oesophageal cancer cells
GSH↓,
LDH↓, FA could promote the release of lactate dehydrogenase (LDH)
ERK↑, A can activate the ERK1/2 pathway
eff↑, conjugated zinc oxide nanoparticles with FA (ZnONPs-FA) to act on hepatoma Huh-7 and HepG2 cells. The results showed that ZnONPs-FA could induce oxidative DNA damage and apoptosis by inducing ROS production.
JAK2↓, by inhibiting the JAK2/STAT6 immune signaling pathway
STAT6↓,
NF-kB↓, thus inhibiting the activation of NF-κB
PYCR1↓, FA can target PYCR1 and inhibit its enzyme activity in a concentration-dependent manner.
PI3K↓, FA inhibits the activation of the PI3K/AKT pathway
Akt↓,
mTOR↓, FA could significantly reduce the expression level of mTOR mRNA and Ki-67 protein in A549 lung cancer graft tissue
Ki-67↓,
VEGF↓,
FGFR1↓, FA is a novel FGFR1 inhibitor
EMT↓, FA can inhibit EMT
CAIX↓, selectively inhibit CAIX
LC3II↑, Autophagy vacuoles and increased LC3-II and p62 autophagy proteins were observed after treatment with this compound
p62↑,
PKM2↓, FA could inhibit the expression of PKM2 and block aerobic glycolysis
Glycolysis↓,
*BioAv↓, FA has poor solubility in water and a poor ability to pass through biological barriers [118]; therefore, the extent to which it is metabolized in vivo after oral administration is largely unknown

2865-

HNK,

Liposomal Honokiol induces ROS-mediated apoptosis via regulation of ERK/p38-MAPK signaling and autophagic inhibition in human medulloblastoma

in-vitro,

MB,

DAOY

vitro+vivo,

NA,

BioAv↓, poor water solubility of HNK results in its low bioavailability, thus limiting its wide use in clinical cancer treatments
BioAv↓, Liposomes can overcome this limitation, and liposomal HNK (Lip-HNK) has promising clinical applications in this aspect
TumCP↓, increased Lip-HNK concentration could inhibit the proliferation of DAOY and D283 cells, without exerting effects on the growth of non-tumor cells
selectivity↑,
P53↑, P53 and P21 proteins (inhibiting cell cycle progression) was increased
P21↑,
CDK4↓, Lip-HNK also downregulated the expression of CDK4 and cyclin D1
cycD1/CCND1↓,
mtDam↑, Lip-HNK caused apoptosis and death, which, in turn, led to the failure of mitochondrial membrane function
ROS↑, Lip-HNK induced ROS production, which, as hypothesized, was blocked by the ROS scavenger NAC
eff↓, Lip-HNK induced ROS production, which, as hypothesized, was blocked by the ROS scavenger NAC
Casp3↑, caspase-3 sectioned and the Bax protein level increased by Lip-HNK
BAX↑,
LC3II↑, LC3BII protein in the Lip-HNK-treated group was noticeably elevated
Beclin-1↑, Beclin-1 (BECN), Atg7 proteins, and LC3BII were dramatically upregulated in the Lip-HNK-treated cells
ATG7↑,
p62↑, Lip-HNK treatment remarkably increased p62 expression, which was dose-dependent
eff↑, Lip-HNK treatment (20 mg/kg) drastically inhibited tumor growth. The combined treatment of Lip-HNK, Chloroquine , and Carboplatin showed more superior antitumor effects
ChemoSen↑, Lip-HNK alone or combined with chemotherapy (Carboplatin or Etoposide) causes significant regression of orthotopic xenografts
*toxicity↓, We also found that Lip-HNK did not damage the liver and kidney

2177-

itraC,

Itraconazole improves survival outcomes in patients with colon cancer by inducing autophagic cell death and inhibiting transketolase expression

Study,

Colon,

present study analyzed extensive data from patients diagnosed with colon cancer using itraconazole between January 2011 and December 2015

in-vitro,

CRC,

COLO205

in-vitro,

CRC,

HCT116

OS↑, Itraconazole increases the 5-year survival rate in patients with late-stage colon cancer who receive chemotherapy
tumCV↓, itraconazole decreased the viability and cell colony formation, and induced cleaved caspase-3 expression and G1 cell cycle arrest of COLO 205 and HCT 116 cells.
Casp3↑,
TumCCA↑,
HH↓, Itraconazole can induce autophagic cell death by activating the hedgehog pathway to inhibit breast cancer cell proliferation (25).
TumAuto↑, expression levels of the autophagy-related proteins, LC3B and p62, significantly increased in COLO 205 and HCT 116 cells following treatment with itraconazole for 24 h
LC3B↑,
p62↑,
TKT↓, TKT expression was decreased following treatment with itraconazole in a time-dependent manner

1709-

Lyco,

Lycopene prevents carcinogen-induced cutaneous tumor by enhancing activation of the Nrf2 pathway through p62-triggered autophagic Keap1 degradation

in-vitro,

Nor,

JB6

mouse cell line

*antiOx↑, Lycopene stimulated the activation of antioxidant enzymes and the translocation of the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) that predominantly maintained intracellular redox equilibrium
*NRF2↑, Lycopene activated the Nrf2 pathway in the presence of carcinogens in vivo and in vitro
*GSH/GSSG↓, Lycopene also rebalanced the GSH/GSSG ratio, partly representing the cellular redox condition commendably
*Catalase↝, catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), and glutathione peroxidase (GPx), lower activities of these enzymes were reversed by this compound
*GR↝,
*SOD↝,
*GPx↝,
*GSH↑, mRNA levels of GSH and these antioxidant substances were also up-regulated significantly by lycopene pretreatment
*Keap1↓, Lycopene induced activation of Nrf2 by reducing Keap1 protein
*p62↑, lycopene induced p62 binding to Keap1, so Keap1 degradation was mediated by p62

227-

MFrot,

MF,

Low Frequency Magnetic Fields Induce Autophagy-associated Cell Death in Lung Cancer through miR-486-mediated Inhibition of Akt/mTOR Signaling Pathway

in-vivo,

Lung,

A549

 0.4T, 7.5 Hz, 4 h/day

 mouse

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↑,
p62↑, blocked p62 degradation
TumCP↓,

1483-

SFN,

Targeting p62 by sulforaphane promotes autolysosomal degradation of SLC7A11, inducing ferroptosis for osteosarcoma treatment

in-vitro,

OS,

143B

0-10uM

in-vitro,

Nor,

HEK293

in-vivo,

OS,

25-50mg/kg

subcutaneous tumor-bearing nude mouse model

AntiCan↑, has shown potential anti-cancer effects with negligible toxicity
*toxicity∅, (liver, kidney, heart, spleen, and lung) showed no evidence of toxicity associated with SFN treatment
Ferroptosis↑, results demonstrate the dependency of downregulation of SLC7A11 in SFN-induced ferroptosis in OS cells
ROS↑, elevated ROS levels, lipid peroxidation, and GSH depletion
lipid-P↑,
GSH↓, which was dependent on decreased levels of SLC7A11
p62↑, enhanced p62/SLC7A11 protein-protein interaction, thereby promoting the lysosomal degradation of SLC7A11 and triggering ferroptosis
SLC12A5↓, SFN induces ferroptosis of OS cells through downregulation of SLC7A11
eff↓, ferroptosis inhibitors Fer-1 (ferrostatin-1), DFO (deferoxamine), and Lip-1 (liproxstatin-1) substantially rescued the cells from SFN-induced cell death
GPx4↓, SFN treatment markedly reduced the expression levels of ferroptosis markers GPX4 and SLC7A11 in OS cells
i-Iron↑, validated the intracellular Fe2+ accumulation by SFN
eff↓, SLC7A11 overexpression notably reversed SFN-induced changes in the ROS level, GSH level, and lipid peroxidation
MDA↑, SFN treatment reduced GSH levels and increased MDA production, indicating the induction of ferroptosis
TumVol↓,
TumW↓,
Ki-67↓, subcutaneous tumors revealed significantly lower expression levels of Ki67, SLC7A11, and GPX4, along with upregulated LC3B in the SFN-treated group
LC3B↑,
*Weight∅, no significant difference in body weight was observed between the control and SFN-treated groups

2009-

SK,

Necroptosis inhibits autophagy by regulating the formation of RIP3/p62/Keap1 complex in shikonin-induced ROS dependent cell death of human bladder cancer

in-vitro,

Bladder,

TumCG↓, shikonin has a selective inhibitory effect on bladder cancer cells
selectivity↑, and has no toxicity on normal bladder epithelial cells
*toxicity∅,
Necroptosis↑, shikonin induced necroptosis and impaired autophagic flux via ROS generation
ROS↑,
p62↑, accumulation of autophagic biomarker p62 elevated p62/Keap1 complex and activated the Nrf2 signaling pathway to fight against ROS
Keap1↑,
*NRF2↑, activated the Nrf2 signaling pathway to fight against ROS
eff↑, we further combined shikonin with late autophagy inhibitor(chloroquine) to treat bladder cancer and achieved a better inhibitory effect.

4869-

Uro,

Urolithin A in Central Nervous System Disorders: Therapeutic Applications and Challenges

Review,

AD,

Review,

Park,

Review,

Stroke,

*MitoP↑, key biological effects of UA, including its promotion of mitophagy and mitochondrial homeostasis, as well as its anti-inflammatory, antioxidant, anti-senescence, and anti-apoptotic properties
*Inflam↓,
*antiOx↑,
*Risk↓, UA’s therapeutic potential in CNS disorders, such as Alzheimer’s disease, Parkinson’s disease, and stroke.
*Aβ↓, UA enhances microglial phagocytosis of Aβ plaques, suppresses neuroinflammation, and reduces tau hyperphosphorylation by restoring mitophagy to eliminate abnormal mitochondria
*p‑tau↓,
*p62↓, In doxorubicin-induced cardiomyopathy mice, UA upregulates p62, LC3-II, PINK1, and Parkin expression, restoring impaired mitophagy, mitigating membrane potential loss and ROS accumulation,
*PARK2↑,
*MMP↑,
*ROS↓,
*Strength↑, Randomized controlled trials in healthy middle-aged and older adults show that oral supplementation with 500–1000 mg of UA significantly improves skeletal muscle endurance and mitochondrial efficiency, reduces plasma inflammatory markers (such as C-r
*CRP↓,
*IL1β↓, UA activates sirtuin 1 (SIRT1)-mediated deacetylation of NF-κB p65, suppressing glial cell activation and the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α)
*IL6↓,
*TNF-α↓,
*AMPK↑, UA enhances brain adenosine 5′-monophosphate-activated protein kinase (AMPK) activation, attenuating NF-κB and MAPK activity, mitigating neuroinflammation, and supporting synaptic recovery
*NF-kB↓,
*MAPK↓,
*p62↑, In a renal ischemia-reperfusion injury model, UA activates the p62—kelch-like ECH-associated protein 1 (Keap1)—nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, boosting superoxide dismutase and catalase activity while lowering ROS levels
*NRF2↑,
*SOD↑,
*Catalase↑,
*HO-1↑, UA upregulates the Keap1-Nrf2/heme oxygenase 1 (HO-1) pathway to inhibit ferroptosis and reduce lipid peroxide accumulation in lung tissue
*Ferroptosis↓,
*lipid-P↓,
*Cartilage↑, reducing cartilage degradation and synovial inflammation
*PI3K↓, UA suppresses the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and Akt/IκB kinase (IKK)/NF-κB signaling pathways, reducing neuronal apoptosis while enhancing BBB integrity and neurological outcomes
*Akt↓,
*mTOR↓,
*Apoptosis↓,
*neuroP↑,
*Bcl-2↓, cerebral artery occlusion model, UA treatment lowers Bcl-2 expression and elevates Bcl-2 associated X protein (Bax) and caspase-3 levels
*BAX↑,
*Casp3↑,
*ATP↑, UA restores mitochondrial membrane potential and ATP production in cardiomyocytes, balancing carnitine palmitoyltransferase1-dependent fatty acid oxidation to reduce apoptosis
*eff↑, in humanized homozygous amyloid beta knockin mice modeling late-onset AD, UA combined with green tea extract (Epigallocatechin gallate) more effectively reduces brain Aβ40 and Aβ42 levels compared to UA alone [106].
*motorD↑, UA administration elevated striatal dopamine levels and enhanced motor coordination, accompanied by suppression of NLRP3 inflammasome activation
*NLRP3↓,
*radioP↑, In a radiation-induced primary astrocyte model, UA activated the PINK1/Parkin-mediated mitophagy pathway, significantly reducing ROS levels in both cells and mitochondria,
*BBB↑, preclinical studies showing that UA primarily crosses the mouse BBB

Showing Research Papers: 1 to 26 of 26

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 26

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

CD8+↑, 1,
Total Targets: 172

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 3, Catalase↑, 1, Catalase↝, 1, Ferroptosis↓, 1, GPx↝, 1, GSH↓, 1, GSH↑, 1, GSH/GSSG↓, 1, HO-1↑, 1, Keap1↓, 1, lipid-P↓, 1, MDA↑, 1, NRF2↑, 3, PARK2↑, 1, ROS↓, 3, ROS↑, 1, SOD↑, 1, SOD↝, 1,

Mitochondria & Bioenergetics ⓘ

ATP↓, 1, ATP↑, 1, MMP↓, 1, MMP↑, 1, MMP∅, 1,

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,

Cell Death ⓘ

Akt↓, 1, Apoptosis↓, 1, BAX↑, 2, Bcl-2↓, 2, Casp3↑, 2, Casp3∅, 1, Cyt‑c∅, 1, Ferroptosis↓, 1, MAPK↓, 1,

Autophagy & Lysosomes ⓘ

LC3II↑, 1, MitoP↑, 1, p62↓, 1, p62↑, 3,

Proliferation, Differentiation & Cell State ⓘ

mTOR↓, 1, PI3K↓, 1,

Migration ⓘ

Cartilage↑, 1, TumCP↓, 1,

Barriers & Transport ⓘ

BBB↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, CRP↓, 1, IL1β↓, 1, IL6↓, 1, Inflam↓, 3, NF-kB↓, 2, TNF-α↓, 1,

Synaptic & Neurotransmission ⓘ

p‑tau↓, 1,

Protein Aggregation ⓘ

Aβ↓, 1, NLRP3↓, 1,

Hormonal & Nuclear Receptors ⓘ

GR↝, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1, eff↓, 1, eff↑, 2,

Clinical Biomarkers ⓘ

CRP↓, 1, IL6↓, 1,

Functional Outcomes ⓘ

motorD↑, 1, neuroP↑, 2, radioP↑, 1, Risk↓, 1, Strength↑, 1, toxicity↓, 1, toxicity∅, 2, Weight∅, 1,
Total Targets: 66

Scientific Paper Hit Count for: p62, p62/sequestosome 1 (SQSTM1)

4 Silver-NanoParticles
3 Curcumin
1 Alpha-Lipoic-Acid
1 Apigenin (mainly Parsley)
1 Metformin
1 Berberine
1 Biochanin A
1 Betulinic acid
1 Bromelain
1 Carnosic acid
1 Trastuzumab
1 Capsaicin
1 Resveratrol
1 Dichloroacetate
1 salinomycin
1 diet FMD Fasting Mimicking Diet
1 Chemotherapy
1 Disulfiram
1 Copper and Cu NanoParticles
1 Ferulic acid
1 Honokiol
1 itraconazole
1 Lycopene
1 Magnetic Field Rotating
1 Magnetic Fields
1 Sulforaphane (mainly Broccoli)
1 Shikonin
1 Urolithin

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#:602  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

p62 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Autophagy & Lysosomes ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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