Key regulators in bee venom-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of ERK and Akt
Key regulators in bee venom-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of ERK and Akt
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DOI：
10.1016/j.intimp.2006.07.027
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发表时间：
2006-12-05
影响因子：
5.6
通讯作者：
Kim, Gi-Young
中科院分区：
文献类型：
--
作者：
Moon, Dong-Oh;Park, Sung-Yong;Kim, Gi-Young
已知蜂毒（BV）抑制癌细胞增殖并诱导癌细胞凋亡。然而，BV诱导的细胞凋亡的分子机制仍然是未知的人类白血病细胞。在本研究中，我们报告BV通过下调ERK和Akt信号通路诱导白血病U937细胞凋亡。此外，BV诱导的细胞凋亡伴随着Bcl-2的下调，caspase-3的激活和随后的聚（ADP-核糖）聚合酶（PARP）裂解。凋亡诱导也伴随着凋亡抑制蛋白（1AP）家族蛋白的下调。Caspase-3抑制剂z-DEVD-favor能够显著恢复细胞活力，并且在Bcl-2过表达细胞中，BV通过Caspase-3激活诱导的凋亡显著减弱。这些结果表明，下调Bcl-2起着重要的作用，在启动作为一个激活剂的半胱天冬酶3参与BV诱导的细胞凋亡。BV还激活p38 MAPK和JNK，下调ERK和Akt。PD 98059（ERK抑制剂）或LY 294002（Akt抑制剂），但不是p38 MAPK和JNK的抑制剂，显着降低细胞活力和增加乳酸脱氢酶（LDH）的释放。结果表明，在BV诱导的人白血病U937细胞凋亡的关键调节因子是Bcl-2和caspase-3，通过下调ERK和Akt信号通路。(c)2006 Elsevier B. V.保留所有权利。
Bee venom (BV) has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in BV-induced apoptosis are still uncharacterized in human leukemic cells. In the present study, we report that BV induces apoptosis in leukemic U937 cells through downregulation of ERK and Akt signal pathway. Furthermore, BV-induced apoptosis was accompanied by downregulation of Bcl-2, activation of caspase-3 and a subsequent poly(ADP-ribose)polymerase (PARP) cleavages. The induction of apoptosis also was accompanied by the downregulation of the inhibitor of apoptosis protein (1AP) family proteins. Caspase-3 inhibitor, z-DEVD-fmk, was significantly capable of restoring cell viability and BV-induced apoptosis through caspase-3 activation was significantly attenuated in Bcl-2-overexpressing cells. These results indicate that downregulation of Bcl-2 plays a major role in the initiation as an activator of a caspase-3 involved with BV-induced apoptosis. BV also triggered the activation of p38 MAPK and JNK, and downregulation of ERK and Akt. PD98059 (an inhibitor of ERK) or LY294002 (an inhibitor of Akt), but not an inhibitor of p38 MAPK and JNK, significantly decreased cell viability and increased lactate dehydrogenase (LDH) release. The results indicated that key regulators in BV-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of the ERK and Akt signal pathway. (c) 2006 Elsevier B.V. All rights reserved.