Side-effects of resveratrol in HepG2 cells: Reduced pten and increased bcl-xl mRNA expression

Abstract

Resveratrol is a natural compound present in red grapes and red wine, and is often consumed in the human diet. The chemopreventive and chemotherapeutic potential of resveratrol in hepatocellular carcinoma (HCC), one of the most common types of liver cancer, has received much attention in recent years. However, the side-effects of resveratrol stimulation are of concern due to the high doses administered to humans. This study investigated the effects of resveratrol on the mRNA expression of pten and bcl-xl in HepG2 cells using semi-quantitative and quantitative PCR. This study demonstrated that 200 µmol/l resveratrol stimulation for 12 h resulted in the inhibition of HepG2 proliferation, reduced pten and increased bcl-xl mRNA expression. The data suggest that (a) the anticancer mechanism of resveratrol does not involve the induction of pten and inhibition of bcl-xl expression and (b) resveratrol induces a cellular self-protection response, which underlies the cellular chemoresistance against resveratrol in HepG2 cells.

Research Article Cytotoxic effects of <i>Vitis</i> <i>labrusca</i> (fox grape) whole juices on human tumor and non-tumor cells, <i>in</i> <i>vitro</i>

“…Resveratrol (3,4',5-trihydroxy-trans-stilbene), a natural polyphenol present in grapes, has been shown to inhibit intestinal tumorigenesis and modulate host-defense-related gene expression in an animal model of human familial adenomatous polyposis (Schneider et al, 2001), in addition to exerting anticancer effects on HepG2 cells (Zheng et al, 2012;Scherzberg et al, 2015), on human nasopharyngeal carcinoma (NPC) (Zhang et al, 2013), colon carcinoma (HT-29) and colorectal carcinoma (CaCo-2) (Scherzberg et al, 2015). Chen et al (2004) reported that resveratrol caused significant cytotoxicity and increased apoptosis and S-phase accumulation of neuroblastoma cells due to the down-regulation of p21 and up-regulation of cyclin E. Resveratrol analogs were efficient in inducing the accumulation of human colon cancer cells in early S-phase of the cell cycle.…”

“…Therefore, the identification of natural compounds with moderate cytotoxic activity is important, due to their easy availability, their low cost, and their ability to act effectively in reducing the incidence of cancer, without adverse side effects (Serra et al, 2013). In this sense, fox grapes (Vitis labrusca) and their derivatives stand out, because of their several nutritional, pharmacological and therapeutic benefits, such as in the treatment of cardiovascular diseases (Quiñones et al, 2013;Huang et al, 2015), liver and kidney disorders (Ulusoy et al, 2012;Charradi et al, 2013;Kim et al, 2013), and anti-tumor activity (Zheng et al, 2012;Zhang et al, 2013;Nivelle et al, 2017), especially due to the presence of phenolic compounds and their antioxidant activity (Fernandes et al, 2013;Maestre et al, 2013;Toaldo et al, 2015;Copetti et al, 2018).…”

Resveratrol suppresses the STAT3 signaling pathway and inhibits proliferation of high glucose-exposed HepG2 cells partly through SIRT1

“…Resveratrol is currently the topic of numerous animal and human studies, and although its anticancer effects have been reported, the underlying mechanism remains to be elucidated (2). During recent research, we found that resveratrol inhibits multiple myeloma cell proliferation and induces apoptosis through downregulation of STAT3 (3), which is a member of the STAT signaling protein family (4).…”

Protective effect of resveratrol against acute lung injury induced by lipopolysaccharide via inhibiting the myd88-dependent Toll-like receptor 4 signaling pathway

“…Resveratrol (3,4' ,5-trihydroxy-trans-stilbene; Rsv), a polyphenol mainly present in grapes and red wine, has numerous bioactivities, including the inhibition of tumor initiation, anti-inflammatory, lipid modification, anti-oxidative, neuroprotective and anti-aging effects (14)(15)(16). Resveratrol has received increasing attention and has been associated with its inhibition of the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) transcription factor (17,18).…”