Inhibitory effects of resveratrol on hepatitis B virus X protein-induced hepatocellular carcinoma

Abstract

Liver cancer occurs very frequently worldwide and hepatocellular carcinoma (HCC) accounts for more than 80% of total primary liver cancer cases. In this study, the anticarcinogenic effects of resveratrol against hepatitis B virus (HBV)-induced HCC were investigated by using HBV X-protein-overexpressing Huh7 (Huh7-HBx) human hepatoma cells. MTT assay showed that resveratrol decreased cell viability. Fluorescence-activated cell-sorter analysis showed that resveratrol induced G1 cell cycle arrest without increasing the sub-G1 phase cell population. Therefore, we evaluated its effect on regulation of cyclin D1, which is critically involved in G1/S transition. Resveratrol lowered cyclin D1 transcription. Western blot analysis of the effects of resveratrol on upstream cyclin D1 transcriptional signaling, extracellular signal-related kinase (ERK), p90RSK, Akt, and p70S6K revealed inhibition of Akt but not the ERK signaling pathway. Collectively, the results indicate that resveratrol inhibits Huh7-HBx proliferation by decreasing cyclin D1 expression through blockade of Akt signaling. We investigated the anticarcinogenic effect and mechanism of resveratrol in xenograft model mice implanted with Huh7-HBx cells. Intraperitoneal resveratrol injection reduced tumor size in the mice. Expression of survivin was reduced, but cyclin D1 was not affected. The results demonstrate that resveratrol treatment may help manage HBV-induced HCC by regulating survivin.

Resveratrol: A Double-Edged Sword in Health Benefits

“…For example, resveratrol and piceid have similar antioxidant capacity, but piceid appears to be more efficacious than resveratrol due to its reaction with its radical form [ 22 , 23 ]. Indeed, resveratrol-glycoside was more effective than resveratrol against hepatitis B virus [ 24 , 25 ]. Piceatannol, with one more hydroxyl group, was already reported as having stronger anti-inflammatory, immunomodulatory, anti-proliferative, anti-leishmanial, anti-leukemic, and protein-tyrosine kinase inhibitory effects [ 19 ].…”

Identification of diagnostic and prognostic biomarkers, and candidate targeted agents for hepatitis B virus‑associated early stage hepatocellular carcinoma based on RNA‑sequencing data

“…Lin et al ( 78 ) reported that resveratrol can promote the recovery of the fatty liver and effectively decrease the incidence of HCC caused by the HBV X protein (HBX) in HBX transgenic mice via downregulating lipogenesis, promoting transient liver regeneration and stimulating antioxidant activity. Additionally, it has been demonstrated that resveratrol has therapeutic effects on HCC through the p53 ( 84 ), cell cycle ( 85 – 87 ). A previous study revealed that menadione kills tumor cells by influencing their redox cycle ( 45 ).…”

Beta-Blockers and Berberine: A Possible Dual Approach to Contrast Neuroblastoma Growth and Progression

“…Natural compounds derived from animals, microorganism, and in particular from plants have been used and have demonstrated significant efficacy in the prevention and treatment of various human disease, including cancer. Various studies have demonstrated that the combination of chemotherapeutic agents and resveratrol (RV), a polyphenol found in red wine with antioxidant, anti-inflammatory [ 55 ], cardioprotective [ 56 ], and anticancer activities [ 57 , 58 ], lead to the inhibition of tumor growth and enhanced antitumor effect compared to chemotherapy alone [ 59 ]. Recently, in vitro and in vivo studies have reported the effects of RV in NB proliferation and progression.…”