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 subsequently 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 by an inhibitor of caspase‐3, Ac‐DEVD‐CHO; and a 17‐kDa active fragment of caspase‐3 was detected following vinblastine treatment, suggesting that caspase‐3 is involved in vinblastine‐induced apoptosis. However, Ac‐DEVD‐CHO affected neither vinblastine‐induced Bcl‐2 phosphorylation nor vinblastine‐induced G2/M arrest. Vinblastine caused G2/M arrest prior to apoptosis, whereas vinblastine‐induced apoptosis was not dependent on the duration of the G2/M phase. Thus, vinblastine‐induced apoptosis might be mediated by the phosphorylation of Bcl‐2, resulting in Bcl‐2 inactivation, and by subsequent activation of caspase‐3.