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Resveratrol exerts its antiproliferative effect on HepG2 hepatocellular carcinoma cells, by inducing cell cycle
George Notas1, Artemissia-Phoebe Nifli, Marilena Kampa
1Laboratories of Gastroenterology, University of Crete School of Medicine, Heraklion, Greece.
Abstract:
The stilbene resveratrol exerts antiproliferative and proapoptotic actions on a number of different cancer cell lines, through diverse mechanisms, including antioxidant effects, enzyme, growth factor and hormone receptor binding, and nucleic acid direct or indirect interactions. Although resveratrol accumulates in the liver, its effect on hepatocellular carcinoma has not been extensively studied. We have used the human hepatocyte-derived cancer cell line HepG2 to address the possible action of resveratrol on cell growth and to examine some possible mechanisms of action. Our results indicate that the stilbene inhibits potently cell proliferation, reduces the production of reactive oxygen species and induces apoptosis, through cell cycle arrest in G1 and G2/M phases. Furthermore it modulates the NO/NOS system, by increasing iNOS and eNOS expression, NOS activity and NO production. Inhibition of NOS enzymes attenuates its antiproliferative effect. These data could be of value in possible prevention or adjuvant treatment of hepatocellular carcinoma, through an increased consumption of resveratrol-rich foods and beverages.
Insights
Resveratrol, a natural stilbene, potently inhibits liver cancer cell growth and promotes apoptosis. It modulates the nitric oxide system, suggesting potential for hepatocellular carcinoma prevention or treatment.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Resveratrol, a stilbene found in grapes and berries, exhibits anticancer properties in various cell lines.
- Its specific effects on hepatocellular carcinoma (HCC) and underlying mechanisms remain underexplored.
- The liver is a primary site for resveratrol accumulation.
Purpose of the Study:
- To investigate the antiproliferative and proapoptotic effects of resveratrol on the human hepatoma cell line HepG2.
- To elucidate the mechanisms of resveratrol's action, focusing on reactive oxygen species (ROS) and the nitric oxide/nitric oxide synthase (NO/NOS) system.
Main Methods:
- Utilized the HepG2 human hepatoma cell line.
- Assessed cell proliferation, ROS production, apoptosis, and cell cycle progression.
- Measured nitric oxide (NO) production and nitric oxide synthase (NOS) enzyme expression and activity (iNOS and eNOS).
Main Results:
- Resveratrol significantly inhibited HepG2 cell proliferation and induced apoptosis.
- It reduced reactive oxygen species (ROS) production and caused cell cycle arrest at G1 and G2/M phases.
- Resveratrol modulated the NO/NOS system by increasing inducible NOS (iNOS) and endothelial NOS (eNOS) expression, NOS activity, and NO production.
- Inhibition of NOS enzymes diminished resveratrol's antiproliferative effect.
Conclusions:
- Resveratrol demonstrates potent antiproliferative and proapoptotic effects on hepatocellular carcinoma cells (HepG2).
- Mechanisms involve ROS reduction, cell cycle arrest, and modulation of the NO/NOS system.
- These findings suggest resveratrol's potential as a preventative or adjuvant therapeutic agent for HCC.
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