Abstract Title:

Induction of apoptosis by withaferin A in human leukemia U937 cells through down-regulation of Akt phosphorylation.

Abstract Source:

Apoptosis. 2008 Nov 11. [Epub ahead of print] PMID: 19002588

Abstract Author(s):

Jung Hwa Oh, Tae-Jin Lee, Sang Hyun Kim, Yung Hyun Choi, Sang Han Lee, Jin Man Lee, Young-Ho Kim, Jong-Wook Park, Taeg Kyu Kwon


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.

Study Type : In Vitro Study

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