Possible mechanisms of paclitaxel-induced apoptosis.

Paclitaxel, a naturally occurring antimicrotubule agent, has been demonstrated to possess significant cell-killing activity in a variety of tumor cells through induction of apoptosis. It is currently unclear whether this finding suggests a novel mechanism of action for paclitaxel against tumor cells or just represents an end product of the well-known action of paclitaxel on 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 arrest. However, this morphological correlation alone does not prove that paclitaxel-induced apoptosis is indeed a secondary event resulting from mitotic arrest. Instead, several lines of evidence obtained from recent studies have suggested that apoptotic cell death induced by paclitaxel may occur via a signaling pathway independent of microtubules and G2/M arrest.