Resveratrol Potently Counteracts Quercetin Starvation‐Induced Autophagy and Sensitizes HepG2 Cancer Cells to Apoptosis

@article{TomsHernndez2018ResveratrolPC,
  title={Resveratrol Potently Counteracts Quercetin Starvation‐Induced Autophagy and Sensitizes HepG2 Cancer Cells to Apoptosis},
  author={Sarah Tom{\'a}s-Hern{\'a}ndez and Jordi Blanco and Cristina Rojas and Joel Roca-Mart{\'i}nez and Mar{\'i}a Jos{\'e} Ojeda-Montes and Ra{\'u}l Beltr{\'a}n-Deb{\'o}n and Santiago Garcia-Vallv{\'e} and Gerard Pujadas and Llu{\'i}s Arola and Miquel Mulero},
  journal={Molecular Nutrition \& Food Research},
  year={2018},
  volume={62},
  pages={\&NA;}
}
SCOPE Resveratrol (RSV) has been described as a potent antioxidant, antisteatotic, and antitumor compound, and it has also been identified as a potent autophagy inducer. On the other hand, quercetin (QCT) is a dietary flavonoid with known antitumor, anti-inflammatory, and antidiabetic effects. Additionally, QCT increases autophagy. To study the hypothetical synergistic effect of both compounds, we test the combined effect of QCT and RSV on the autophagy process in HepG2 cells. METHODS AND… 

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References

SHOWING 1-10 OF 63 REFERENCES
Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition
TLDR
It is demonstrated that resveratrol induces autophagy by directly inhibiting the mTOR-ULK1 pathway and proposed mTOR as a novel direct target of resver atrol, and inhibition of mTOR is necessary for Autophagy induction.
Quercetin induces protective autophagy in gastric cancer cells: Involvement of Akt-mTOR- and hypoxia-induced factor 1α-mediated signaling
TLDR
Functional studies revealed that quercetin activated autophagy by modulation of Akt-mTOR signaling and hypoxia-induced factor 1α (HIF-1α) signaling, and a xenograft model provided additional evidence for occurrence of quercETin-induced apoptosis and Autophagy in vivo.
Resveratrol improves hepatic steatosis by inducing autophagy through the cAMP signaling pathway.
TLDR
RSV improved hepatic steatosis partially by inducing autophagy via the cAMP-PRKA-AMPK-SIRT1 signaling pathway, which provides new evidence regarding RSV's effects on NAFLD treatment.
Quercetin Induces Mitochondrial Mediated Apoptosis and Protective Autophagy in Human Glioblastoma U373MG Cells
TLDR
Pretreatment with chloroquine, an autophagy inhibitor, strongly augmented apoptosis in U373MG cells, indicating that quercetin induced protective autopagy in U 373MG cells.
Quercetin, a Natural Flavonoid Interacts with DNA, Arrests Cell Cycle and Causes Tumor Regression by Activating Mitochondrial Pathway of Apoptosis
TLDR
It is found that quercetin interacts with DNA directly, and could be one of the mechanisms for inducing apoptosis in both, cancer cell lines and tumor tissues by activating the intrinsic pathway.
Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation.
TLDR
These results provide new insight regarding the possible molecular mechanisms of quercetin and suppresses oxLDL-induced endothelial oxidative injuries by activating SIRT1 and modulating the AMPK/NADPH oxidase/AKT/endothelial NO synthase signaling pathway.
Resveratrol Enhances Palmitate-Induced ER Stress and Apoptosis in Cancer Cells
TLDR
It is suggested that RSV exerts its cytotoxic role in cancer cells exposed to a saturated FA context primarily by triglyceride accumulation inhibition, probably leading to an intracellular palmitate accumulation that triggers a lipid-mediated cell death.
Quercetin simultaneously induces G0/G1‐phase arrest and caspase‐mediated crosstalk between apoptosis and autophagy in human leukemia HL‐60 cells
TLDR
It was found that use of the autophagy inhibitor, 3‐methyladenine, significantly enhanced quercetin‐mediated apoptotic cell death as analyzed by MTS and DNA fragmentation assays, and pretreatment of HL‐60 cells with the pan‐caspase inhibitor, Z‐VAD‐fmk, dramatically reversed quercETin‐ mediated apoptotic and autophagic cell death.
Regulation of autophagy by polyphenolic compounds as a potential therapeutic strategy for cancer
TLDR
The capacity of these polyphenolic compounds to provide a means of cancer cell death that enhances the effects of standard therapies should be taken into consideration for designing novel therapeutic strategies.
...
...