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

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Title Mahanine reverses an epigenetically silenced tumor suppressor gene RASSF1A in human prostate cancer cells
 
Creator Jagadeesh, S
Sinha, S
Pal, BC
Bhattacharya, S
Banerjee, PP
 
Subject Biochemistry & Molecular Biology; Biophysics
 
Description 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. (C) 2007 Published by Elsevier Inc.
 
Publisher ACADEMIC PRESS INC ELSEVIER SCIENCESAN DIEGO525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
 
Date 2011-09-20T12:12:30Z
2011-09-20T12:12:30Z
2007
 
Type Article
 
Identifier BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
0006-291X
http://hdl.handle.net/123456789/14300
 
Language English