Abstract
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-γ1 cleavage by withaferin A. Taken together, our results indicated that the JNK and Akt pathways and inhibition of NF-κB activity were key regulators of apoptosis in response to withaferin A in human leukemia U937 cells.
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Acknowledgment
This work was supported by the Korea Science and Engineering Foundation through the MRC at Keimyung University (R13-2002-028-03001-0).
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Oh, J.H., Lee, TJ., Kim, S.H. et al. Induction of apoptosis by withaferin A in human leukemia U937 cells through down-regulation of Akt phosphorylation. Apoptosis 13, 1494–1504 (2008). https://doi.org/10.1007/s10495-008-0273-y
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DOI: https://doi.org/10.1007/s10495-008-0273-y