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Induction of apoptosis by withaferin A in human leukemia U937 cells through down-regulation of Akt phosphorylation |
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| Authors: | 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 |
| Institution: | 1. Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu, 700-712, South Korea 2. Department of Anatomy, College of Medicine, Yeungnam University, Taegu, 705-717, South Korea 3. Deaprtment of Pharmacology, School of Medicine, Kyungpook National University, Taegu, 700-422, South Korea 4. Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan, South Korea 5. Department of Food Sciences and Technology, Kyungpook National University, Taegu, 702-701, South Korea 6. Department of Food Sciences and Technology, Hoseo University, Ansan, 336-795, South Korea 7. Department of Molecular Biology and Immunology, College of Medicine, Kosin University, Busan, South Korea |
| 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. |
| Keywords: | Withaferin A Apoptosis pAkt U937 JNK XIAP |
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