Tashiro E, Simizu S, Takada M, Umezawa K, Imoto M
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama.
Jpn J Cancer Res. 1998 Sep;89(9):940-6. doi: 10.1111/j.1349-7006.1998.tb00652.x.
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.
长春花碱使细胞停滞于细胞周期的G2/M期，随后通过凋亡诱导细胞死亡。我们发现用长春花碱处理细胞会诱导Bcl-2磷酸化，导致Bcl-2与Bax解离。此外，caspase-3抑制剂Ac-DEVD-CHO可抑制长春花碱诱导的凋亡；长春花碱处理后检测到一个17 kDa的caspase-3活性片段，表明caspase-3参与长春花碱诱导的凋亡。然而，Ac-DEVD-CHO既不影响长春花碱诱导的Bcl-2磷酸化，也不影响长春花碱诱导的G2/M期停滞。长春花碱在凋亡之前引起G2/M期停滞，而长春花碱诱导的凋亡并不依赖于G2/M期的持续时间。因此，长春花碱诱导的凋亡可能是由Bcl-2磷酸化介导，导致Bcl-2失活，并随后激活caspase-3。
