Sustained activation of p34(cdc2) is required for noscapine-induced apoptosis.
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 p34(cdc2) activity with olomoucine in FM3A murine mammary carcinoma cells or by reducing the level and activity of p34(cdc2) in a mutant cell line FT210 derived from FM3A. Furthermore, transfection of the mutant FT210 cells with wild-type p34(cdc2) restored their ability to undergo mitotic arrest and then apoptosis in response to noscapine. Thus, we conclude that sustained activation of the p34(cdc2) kinase during mitotic arrest is required for subsequent apoptosis induced by noscapine, establishing a link between the two events.
Ye
K
K
Department of Cell Biology, Emory University School of Medicine, 1648 Pierce Dr., Atlanta, GA 30322, USA.
Zhou
J
J
Landen
J W
JW
Bradbury
E M
EM
Joshi
H C
HC
D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D000996:Antitussive Agents / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000494:pharmacology; D051379:Mice; D008938:Mitosis; D009154:Mutation; D009665:Noscapine / Q000494:pharmacology*; D010957:Plasmids / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D017304:Annexin A5; D000996:Antitussive Agents; D005456:Fluorescent Dyes; D009665:Noscapine; D011494:Protein Kinases; C102333:histone H1 kinase; D016203:CDC2 Protein Kinase