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Bcl-2 modulates resveratrol-induced ROS production by regulating mitochondrial respiration in tumor cells

Ivan Cherh Chiet Low1, Zhi Xiong Chen, Shazib Pervaiz

  • 1Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Antioxidants & Redox Signaling
|April 7, 2010
PubMed

Insights

Resveratrol induces cell death in leukemia cells by increasing mitochondrial oxidative stress. Bcl-2 protein overexpression protects leukemia cells by reducing this stress, highlighting a novel survival mechanism.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Cancer Research

Background:

  • Resveratrol, a natural flavonoid, exhibits anti-cancer properties.
  • Its mechanism involves inducing apoptosis in tumor cells, including leukemia.
  • The role of mitochondrial metabolism and Bcl-2 in this process requires further elucidation.

Purpose of the Study:

  • To investigate resveratrol's impact on human leukemia cell lines.
  • To determine resveratrol's effect on intracellular reactive oxygen species (ROS) production.
  • To examine the influence of Bcl-2 overexpression on resveratrol-induced cellular responses.

Main Methods:

  • Exposure of CEM leukemia cells to varying resveratrol concentrations.
  • Assessment of mitochondrial superoxide production and transmembrane potential.
  • Analysis of cell viability, mitochondrial respiration, and Complex IV activity.
  • Investigation of Bcl-2 overexpression and siRNA-mediated gene silencing effects.

Main Results:

  • Resveratrol increased mitochondrial superoxide production and decreased cell viability in CEM cells.
  • Bcl-2 overexpression enhanced mitochondrial respiration but attenuated resveratrol's ROS-inducing effects.
  • CEM/Bcl-2 cells showed reduced mitochondrial respiration and superoxide production upon resveratrol treatment, promoting survival.
  • siRNA targeting Bcl-2 reversed its inhibitory effect on resveratrol-induced ROS production.

Conclusions:

  • Mitochondrial metabolism plays a crucial role in resveratrol's anti-leukemia activity.
  • Bcl-2 offers a novel mechanism of protection against resveratrol-induced oxidative stress by modulating mitochondrial respiration.
  • This highlights Bcl-2's role in fine-tuning mitochondrial function for cell survival under stress.

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