Mahanine InhibitsGrowth and InducesApoptosis in ProstateCancerCellsThroughtheDeactivation of Akt andActivation ofCaspases

Sinha, Swati and Pal, Bikas C and Jagadeesh, Shankar and Banerjee, Partha P and Bandyopadhaya, Arun and Bhattacharya, Samir (2006) Mahanine InhibitsGrowth and InducesApoptosis in ProstateCancerCellsThroughtheDeactivation of Akt andActivation ofCaspases. The Prostate, 66 (12). pp. 1257-1265.

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    Abstract

    The present study was undertaken to evaluate anti-proliferative and - apoptotic activities of mahanine, a plant derived carbazole alkaloid, in prostate cancer cells and to determine its molecular mechanism by which it induces apoptotic cell death. The growth inhibitory and apoptotic inductive effect of mahanine on prostate cancer cells were examined by measuring cell proliferation and BrdU labeling, caspase activity, DNA fragmentation, and Western blot analyses. Mahanine inhibited growth of PC3 and LNCaP prostate cancer cells in a dose and time-dependent manner. Mechanistically, mahanine inhibited cell-survival pathway by dephosphorylation of PIP3 dependent kinase 1 (PDK1) thereby deactivation of Akt and downregulation of Bcl-xL. In addition, mahanine activated caspase pathway (caspases 9 and 3) and eventually cleavage of DNA repair enzyme, PARP resulting DNA fragmentation and apoptosis. Mahanine inhibits growth and induces apoptosis in both androgenresponsive, LNCaP and androgen-independent, PC3 cells by targeting cell survival pathway. Prostate 66: 1257–1265, 2006. #2006 Wiley-Liss, Inc.

    Item Type: Article
    URI: http://www.eprints.iicb.res.in/id/eprint/483
    Subjects: Cell Biology & Physiology
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Ms Sutapa Ganguly
    Date Deposited: 02 Nov 2011 12:35
    Last Modified: 07 Feb 2012 11:46
    Official URL: http://dx.doi.org/
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