Caspase-3 activation is not responsible for vinblastine-induced Bcl-2 phosphorylation and G2/M arrest in human small cell lung carcinoma Ms-1 cells

Vinblastine arrests cells in the G2/M phase of the cell cycle and subsequen tly induces cell death by apoptosis. We found that treatment of cells with vinblastine induced phosphorylation of Bcl-2, resulting in the dissociation of Bcl-2 and Bax. Moreover, vinblastine-induced apoptosis was suppressed b y an inhibitor of caspase-3, Ac-DEVD-CHO; and a 17-kDa active fragment of c aspase-3 was detected following vinblastine treatment, suggesting that casp ase-3 is involved in vinblastine-induced apoptosis. However, Ac-DEVD-CHO af fected neither vinblastine-induced Bcl-2 phosphorylation nor vinblastine-in duced G2/M arrest. Vinblastine caused G2/M arrest prior to apoptosis, where as vinblastine-induced apoptosis was not dependent on the duration of the G 2/M phase. Thus, vinblastine-induced apoptosis might be mediated by the pho sphorylation of Bcl-2, resulting in Bcl-2 inactivation, and by subsequent a ctivation of caspase-3.