Paclitaxel induces release of cytochrome c from mitochondria isolated fromhuman neuroblastoma cells

Paclitaxel Is an antimicrotubule agent that induces mitotic block and apopt osis, We show for the first time that paclitaxel acts directly on mitochond ria isolated from human cancer cells. In isolated yeast mitochondria, pacli taxel (15 mu M) induced an 18% increase in the respiration rate, with no co ncomitant release of cytochrome c. In isolated neuroblastoma mitochondria, paclitaxel (10-100 mu M) induced a 27-72% release of cytochrome c. Release was prevented by cyclosporin A, suggesting the involvement of the permeabil ity transition pore. Doxorubicin did not induce cytochrome c release, where as vinorelbine, another antimicrotubule agent, did. Thus, antimicrotubule a gents can directly affect mitochondria to induce apoptosis.