Sustained Activation of p34 cdc2 Is Required for Noscapine-induced Apoptosis

Abstract Mitotic arrest and subsequent apoptosis has been observed in many types of cells treated with anti-microtubule agents. However, the molecular mechanisms underlying the two events as well as their relationship are not well understood; on the contrary, there has been increasing evidence indicating that anti-microtubule agents might induce apoptosis via signaling pathways independent of mitosis. In this study, we found that apoptosis induced by noscapine, an anti-microtubule drug previously shown to cause both mitotic arrest and apoptotic cell death, was blocked by inhibiting p34cdc2activity with olomoucine in FM3A murine mammary carcinoma cells or by reducing the level and activity of p34cdc2 in a mutant cell line FT210 derived from FM3A. Furthermore, transfection of the mutant FT210 cells with wild-type p34cdc2 restored their ability to undergo mitotic arrest and then apoptosis in response to noscapine. Thus, we conclude that sustained activation of the p34cdc2 kinase during mitotic arrest is required for subsequent apoptosis induced by noscapine, establishing a link between the two events.