Induction of apoptosis by withaferin A in human leukemia U937 cells through down-regulation of Akt phosphorylation
- Affiliated Author(s)
- 박종욱; 권택규
- Alternative Author(s)
- Park, Jong Wook; Kwon, Taeg Kyu
- Journal Title
- Issued Date
- 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-c1 cleavage by
withaferin A. Taken together, our results indicated that the
JNK and Akt pathways and inhibition of NF-jB activity
were key regulators of apoptosis in response to withaferin
A in human leukemia U937 cells.
Keywords Withaferin A Apoptosis pAkt U937
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