Mahanine reverses an epigenetically silenced tumor suppressor gene RASSF1A in human prostate cancer cells.

Abstract	It is becoming clear that frequent epigenetic silencing of tumor suppressor genes could be responsible for the development of cancer in various organs. Several recent reports suggest that suppression of RASSF1A is associated with the advanced grade and stage of prostate cancer and many other cancers. In this investigation, we demonstrated that, mahanine, a plant derived carbazole alkaloid, induced RASSF1A expression in both androgen-responsive (LNCaP) and androgen-negative (PC3) prostate cancer cells by inhibiting DNA methyltransferase (DNMT) activity. Mahanine-induced expression of RASSF1A in turn significantly reduced cyclin D1 but not other cyclins. To understand the inverse relationship between RASSF1A and cyclin D1, we observed that mahanine treatment down-regulates cyclin D1 and addition of RASSF1A siRNA prevented this inhibition. This study show for the first time that mahanine can reverse an epigenetically silenced gene, RASSF1A in prostate cancer cells by inhibiting DNMT activity that in turn down-regulates a key cell cycle regulator, cyclin D1. Mahanine therefore, promises an encouraging therapeutic choice for advanced prostatic cancer.
Authors	Shankar Jagadeesh, Swati Sinha, Bikas C Pal, Samir Bhattacharya, Partha P Banerjee
Journal	Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 362 Issue 1 Pg. 212-217 (Oct 12 2007) ISSN: 0006-291X [Print] United States
PMID	17698033 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Alkaloids Carbazoles RASSF1 protein, human Tumor Suppressor Proteins mahanine Cyclin D1 DNA (Cytosine-5-)-Methyltransferases
Topics	Alkaloids (metabolism) Carbazoles (metabolism, pharmacology) Cell Line, Tumor Cyclin D1 (metabolism) DNA (Cytosine-5-)-Methyltransferases (metabolism) Dose-Response Relationship, Drug Down-Regulation Epigenesis, Genetic Gene Expression Regulation, Neoplastic Gene Silencing Humans Male Prostatic Neoplasms (genetics, metabolism) Tumor Suppressor Proteins (genetics, physiology)

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