Aspirin induces apoptosis through release of cytochrome c from mitochondria

Nonsteroidal anti-inflammatory drugs (NSAID) reduce the risk for cancer, du e to their antiproliferative and apoptosis-inducing effects. A critical pat hway for apoptosis Involves the release of cytochrome c from mitochondria, which then interacts with Apaf-1 to activate caspase proteases that orchest rate cell death, In this study we found that treatment of a human cancer ce ll line with aspirin induced caspase activation and the apoptotic cell morp hology, which was blocked by the caspase inhibitor zVAD-fmk. Further analys is of the mechanism underlying this apoptotic event showed that aspirin ind uces translocation of Bax to the mitochondria and triggers release of cytoc hrome c into the cytosol. The release of cytochrome c from mitochondria was inhibited by overexpression of the antiapoptotic protein Bcl-2 and cells t hat lack Apaf-1 were resistant to aspirin-induced apoptosis, These data pro vide evidence that the release of cytochrome c is an important part of the apoptotic mechanism of aspirin.