Tamoxifen Induces Oxidative Stress and Mitochondrial Apoptosis via Stimulating Mitochondrial Nitric Oxide Synthase
Open Access
- 1 February 2007
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 67 (3) , 1282-1290
- https://doi.org/10.1158/0008-5472.can-06-3099
Abstract
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 Ca2+ 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. [Cancer Res 2007;67(3):1282–90]Keywords
This publication has 51 references indexed in Scilit:
- Long-term modulation of mitochondrial Ca2+ signals by protein kinase C isozymesThe Journal of cell biology, 2004
- Mitochondrial calcium uptake stimulates nitric oxide production in mitochondria of bovine vascular endothelial cellsAmerican Journal of Physiology-Cell Physiology, 2004
- Elevation of mitochondrial glutathione by γ‐glutamylcysteine ethyl ester protects mitochondria against peroxynitrite‐induced oxidative stressJournal of Neuroscience Research, 2003
- Mitochondria and Nitric OxideAntioxidants and Redox Signaling, 2003
- Mitochondria as targets for established and novel anti-cancer agentsDrug Resistance Updates, 2001
- Tamoxifen but Not 4-Hydroxytamoxifen Initiates Apoptosis in p53(−) Normal Human Mammary Epithelial Cells by Inducing Mitochondrial DepolarizationPublished by Elsevier ,2001
- Mitochondrial Nitric Oxide Synthase, Oxidative Stress and ApoptosisNeurosignals, 2001
- Oxidative Damage and Tyrosine Nitration from PeroxynitriteChemical Research in Toxicology, 1996
- Conditions that lithium inhibits or potentiates vasopressin V1 receptor-mediated platelet aggregation and [Ca++]i mobilizationGeneral Pharmacology: The Vascular System, 1995
- Drug toxicity mechanisms in human hepatoma HepG2 cells: cyclosporin A and tamoxifenXenobiotica, 1995