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  • Title: Induction of apoptosis by withaferin A in human leukemia U937 cells through down-regulation of Akt phosphorylation.
    Author: Oh JH, Lee TJ, Kim SH, Choi YH, Lee SH, Lee JM, Kim YH, Park JW, Kwon TK.
    Journal: Apoptosis; 2008 Dec; 13(12):1494-504. PubMed ID: 19002588.
    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-gamma1 cleavage by withaferin A. Taken together, our results indicated that the JNK and Akt pathways and inhibition of NF-kappaB activity were key regulators of apoptosis in response to withaferin A in human leukemia U937 cells.
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