Mahanine inhibits growth and induces apoptosis in prostate cancer cells through the deactivation of Akt and activation of caspases.

Abstract

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.

• Authors: Swati Sinha, Bikas C Pal, Shankar Jagadeesh, Partha P Banerjee, Arun Bandyopadhaya, Samir Bhattacharya
• Journal: The Prostate (Prostate) Vol. 66 Issue 12 Pg. 1257-65 (Sep 01 2006) ISSN: 0270-4137 [Print] United States
• PMID: 16683271 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2006 Wiley-Liss, Inc.

Chemical References

• BCL2L1 protein, human
• Carbazoles
• DNA, Neoplasm
• Toxoids
• bcl-X Protein
• mahanine
• 3-Phosphoinositide-Dependent Protein Kinases
• PDPK1 protein, human
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt
• CASP3 protein, human
• CASP9 protein, human
• Caspase 3
• Caspase 9
• Caspases

Topics

• 3-Phosphoinositide-Dependent Protein Kinases
• Apoptosis (drug effects)
• Carbazoles (pharmacology)
• Caspase 3
• Caspase 9
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA Fragmentation
• DNA, Neoplasm (genetics)
• Dose-Response Relationship, Drug
• Enzyme Activation (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Male
• Prostatic Neoplasms (genetics, pathology, physiopathology)
• Protein Serine-Threonine Kinases (physiology)
• Proto-Oncogene Proteins c-akt (drug effects, physiology)
• Signal Transduction (drug effects, physiology)
• Time Factors
• Toxoids (pharmacology)
• bcl-X Protein (physiology)