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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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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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Authors and Affiliations

  1. Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu, 700-712, South Korea

    Jung Hwa Oh, Jong-Wook Park & Taeg Kyu Kwon

  2. Department of Anatomy, College of Medicine, Yeungnam University, Taegu, 705-717, South Korea

    Tae-Jin Lee

  3. Deaprtment of Pharmacology, School of Medicine, Kyungpook National University, Taegu, 700-422, South Korea

    Sang Hyun Kim

  4. Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan, South Korea

    Yung Hyun Choi

  5. Department of Food Sciences and Technology, Kyungpook National University, Taegu, 702-701, South Korea

    Sang Han Lee

  6. Department of Food Sciences and Technology, Hoseo University, Ansan, 336-795, South Korea

    Jin Man Lee

  7. Department of Molecular Biology and Immunology, College of Medicine, Kosin University, Busan, South Korea

    Young-Ho Kim

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  1. Jung Hwa Oh
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Correspondence to Taeg Kyu Kwon.

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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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