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Mahanine inhibits growth and induces apoptosis in prostate cancer cells through the deactivation of Akt and activation of caspases
Author(s) -
Sinha Swati,
Pal Bikas C.,
Jagadeesh Shankar,
Banerjee Partha P.,
Bandyopadhaya Arun,
Bhattacharya Samir
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20415
Subject(s) - lncap , apoptosis , protein kinase b , cancer research , dna fragmentation , prostate cancer , cell growth , caspase , programmed cell death , cancer cell , biology , microbiology and biotechnology , pi3k/akt/mtor pathway , chemistry , cancer , biochemistry , genetics
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS Mahanine inhibits growth and induces apoptosis in both androgen‐responsive, LNCaP and androgen‐independent, PC3 cells by targeting cell survival pathway. Prostate © 2006 Wiley‐Liss, Inc.