Sinha Swati, Pal Bikas C, Jagadeesh Shankar, Banerjee Partha P, Bandyopadhaya Arun, Bhattacharya Samir
Indian Institute of Chemical Biology, Kolkata, India.
Prostate. 2006 Sep 1;66(12):1257-65. doi: 10.1002/pros.20415.
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 androgen-responsive, LNCaP and androgen-independent, PC3 cells by targeting cell survival pathway.
本研究旨在评估植物源咔唑生物碱马汉宁对前列腺癌细胞的抗增殖和抗凋亡活性，并确定其诱导凋亡性细胞死亡的分子机制。
通过测量细胞增殖、BrdU标记、半胱天冬酶活性、DNA片段化和蛋白质免疫印迹分析，检测马汉宁对前列腺癌细胞的生长抑制和凋亡诱导作用。
马汉宁以剂量和时间依赖性方式抑制PC3和LNCaP前列腺癌细胞的生长。机制上，马汉宁通过使磷脂酰肌醇-3,4,5-三磷酸依赖激酶1（PDK1）去磷酸化来抑制细胞存活途径，从而使Akt失活并下调Bcl-xL。此外，马汉宁激活半胱天冬酶途径（半胱天冬酶9和3），最终切割DNA修复酶聚（ADP-核糖）聚合酶（PARP），导致DNA片段化和细胞凋亡。
马汉宁通过靶向细胞存活途径抑制雄激素反应性LNCaP细胞和雄激素非依赖性PC3细胞的生长并诱导其凋亡。
