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.

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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