Aspirin Induces Apoptosis through Release of Cytochrome c from Mitochondria

• Main Authors: Katja C. Zimmermann, Nigel J. Waterhouse, Joshua C. Goldstein, Martin Schuler, Douglas R. Green
• Format: Article
• Language: English
• Published: Elsevier 2000-01-01
• Series: Neoplasia: An International Journal for Oncology Research
• Subjects: aspirin; apoptosis; cytochrome c; mitochondria; NSAID
• Online Access: http://www.sciencedirect.com/science/article/pii/S147655860080041X

Nonsteroidal anti-inflammatory drugs (NSAID) reduce the risk for cancer, due to their anti proliferative and apoptosis-inducing effects. A critical pathway for apoptosis involves the release of cytochrome c from mitochondria, which then interacts with Apaf-1 to activate caspase proteases that orchestrate cell death. In this study we found that treatment of a human cancer cell line with aspirin induced caspase activation and the apoptotic cell morphology, which was blocked by the caspase inhibitor zVAD-fmk. Further analysis of the mechanism underlying this apoptotic event showed that aspirin induces translocation of Bax to the mitochondria and triggers release of cytochrome c into the cytosol. The release of cytochrome c from mitochondria was inhibited by overexpression of the antiapoptotic protein Bcl-2 and cells that lack Apaf-1 were resistant to aspirin-induced apoptosis. These data provide evidence that the release of cytochrome c is an important part of the apoptotic mechanism of aspirin.