Induction of apoptosis by withaferin A in human leukemia U937 cells through down-regulation of Akt phosphorylation
Induction of apoptosis by withaferin A in human leukemia U937 cells through down-regulation of Akt phosphorylation
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DOI：
10.1007/s10495-008-0273-y
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发表时间：
2008-12-01
期刊：
影响因子：
7.2
通讯作者：
Kwon, Taeg Kyu
中科院分区：
文献类型：
--
作者：
Oh, Jung Hwa;Lee, Tae-Jin;Kwon, Taeg Kyu
睡茄素A是睡茄的主要化学成分，具有抑制肿瘤细胞生长、抗肿瘤、抑制肿瘤转移和血管生成的作用。醉茄素A启动细胞凋亡的机制仍然知之甚少。在本报告中，我们研究了醉茄素A对U937人前单核细胞凋亡途径的影响。我们发现，醉茄素A诱导凋亡与caspase-3的激活。JNK和Akt信号通路在Withaferin A诱导U937细胞凋亡中起重要作用。此外，我们已经表明，Bcl-2和活性Akt（myr-Akt）在U937细胞中的过表达抑制了凋亡的诱导，caspase-3的激活，以及由醉茄素A引起的PLC-γ 1裂解。总之，我们的结果表明，JNK和Akt途径和NF-κ B B活性的抑制是响应于醉茄素A的人白血病U937细胞凋亡的关键调节因子。
Withaferin A, a major chemical constituent of Withania somnifera, has been reported for its tumor cell growth inhibitory activity, antitumor effects, and impairing metastasis and angiogenesis. The mechanism by which withaferin A initiates apoptosis remains poorly understood. In the present report, we investigated the effect of withaferin A on the apoptotic pathway in U937 human promonocytic cells. We show that withaferin A induces apoptosis in association with the activation of caspase-3. JNK and Akt signal pathways play crucial roles in withaferin A-induced apoptosis in U937 cells. Furthermore, we have shown that overexpression of Bcl-2 and active Akt (myr-Akt) in U937 cells inhibited the induction of apoptosis, activation of caspase-3, and PLC-gamma 1 cleavage by withaferin A. Taken together, our results indicated that the JNK and Akt pathways and inhibition of NF-kappa B activity were key regulators of apoptosis in response to withaferin A in human leukemia U937 cells.