Possible mechanisms of paclitaxel-induced apoptosis

Paclitaxel, a naturally occurring antimicrotubule agent, has been demonstra ted to possess significant cell-killing activity in a variety of tumor cell s through induction of apoptosis. It is currently unclear whether this find ing suggests a novel mechanism of action for paclitaxel against tumor cells or just represents an end product of the well-known action of paclitaxel o n microtubules and cell cycle arrest. Morphologically, a sustained block of mitosis seems to be required for paclitaxel-induced apoptosis because most apoptotic events are observed to occur in cells showing a prior mitotic ar rest. However, this morphological correlation alone does not prove that pac litaxel-induced apoptosis is indeed a secondary event resulting from mitoti c arrest. Instead, several lines of evidence obtained from recent studies h ave suggested that apoptotic cell death induced by paclitaxel may occur via a signaling pathway independent of microtubules and G(2)/M arrest. BIOCHEM PHARMACOL 57;11:1215-1221, 1999. (C) 1999 Elsevier Science Inc.