Vijayalakshmi Krishnamurthy

Mitochondrion plays an important role in cellular metabolism and in energy production. Free radicals contribute damage to mitochondria during various pathological conditions. Tamoxifen is an anti-estrogen drug given to treat breast cancer. Tamoxifen and its metabolites induce varied cellular effects. It was therefore planned to study the impact of tamoxifen on mitochondria to observe its mechanism of action in promoting cell death. Mitochondrion was isolated from sheep liver and different concentrations of tamoxifen were added to study its impact on oxidative stress. Tamoxifen induced swelling of mitochondria which in turn produced lipid peroxides in a dose-dependent manner. Tamoxifen significantly increased the levels of nitrite and nitrate in mitochondria with depletion of glutathione. It was observed that tamoxifen increased NADH oxidation leading to the release of calcium from mitochondria. These changes observed are correlated with the mechanism of action of tamoxifen in treating breast cancer.