Breast Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Breast Cancer, including details on symptoms, genetics, screening, treatment, information.

Tamoxifen induces oxidative stress and mitochondrial apoptosis via stimulating mitochondrial nitric oxide synthase.

Nazarewicz RR, Zenebe WJ, Parihar A, Larson SK, Alidema E, Choi J, Ghafourifar P

Vascular Surgery, Davis Heart and Lung Research Institute, and Institute of Mitochondrial Biology, Ohio State University Medical Center, 473 West 12th Avenue, Columbus, OH 43210, USA.

Tamoxifen is an anticancer drug that induces oxidative stress and apoptosis via mitochondria-dependent and nitric oxide (NO)-dependent pathways. The present report shows that tamoxifen increases intramitochondrial ionized Ca(2+) concentration and stimulates mitochondrial NO synthase (mtNOS) activity in the mitochondria from rat liver and human breast cancer MCF-7 cells. By stimulating mtNOS, tamoxifen hampers mitochondrial respiration, releases cytochrome c, elevates mitochondrial lipid peroxidation, increases protein tyrosine nitration of certain mitochondrial proteins, decreases the catalytic activity of succinyl-CoA:3-oxoacid CoA-transferase, and induces aggregation of mitochondria. The present report suggests a critical role for mtNOS in apoptosis induced by tamoxifen.

Published 6 February 2007 in Cancer Res, 67(3): 1282-90.
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