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

Identifier:  imarina:3647439

Handle: https://hdl.handle.net/20.500.11797/imarina3647439

Authors:  Tomas-Hernandez, Sarah; Blanco, Jordi; Rojas, Cristina; Roca-Martinez, Joel; Jose Ojeda-Montes, Maria; Beltran-Debon, Raul; Garcia-Vallve, Santiago; Pujadas, Gerard; Arola, Lluis; Mulero, Miquel

Abstract:
Resveratrol (RSV) has been described as a potent antioxidant, anti-steatotic, 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 tested the combined effect of QCT and RSV on the autophagy process in HepG2 cells METHODS AND RESULTS: Autophagy was studied by western blotting, real-time RT-PCR, and cellular staining. Our results clearly indicate a bifunctional molecular effect of RSV. Both polyphenols were individually able to promote autophagy. Strikingly, when RSV was combined with QCT, it promoted a potent reduction of QCT-induced autophagy and influenced pro-apoptotic signaling. Conclusion: RSV acts differentially on the autophagic process depending on the cellular energetic state. We further characterized the molecular mechanisms related to this effect, and we observed that AMP-activated protein kinase (AMPK) phosphorylation, heme oxygenase 1 (HO-1) downregulation, lysosomal membrane permeabilization (LMP) and Zinc (Zn2+ ) dynamics could be important modulators of such RSV-related effects and could globally represent a promising strategy to sensitize cancer cells to QCT treatment. This article is protected by copyright. All rights reserved.