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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, Shankar
Sinha, Swati
Pal, Bikas C
Bhattacharya, Samir
Banerjee, Partha P
 
Subject Chemistry
 
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.
� 2007 Published by Elsevier Inc.
 
Date 2007
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1050/1/BIOCHEMICAL_AND_BIOPHYSICAL_RESEARCH_COMMUNICATIONS__362_(1)_212%2D217;2007[27].pdf
Jagadeesh, Shankar and Sinha, Swati and Pal, Bikas C and Bhattacharya, Samir and Banerjee, Partha P (2007) Mahanine Reverses an Epigenetically Silenced Tumor Suppressor Gene RASSF1A in Human Prostate Cancer Cells. Biochemical and Biophysical Research Communications, 362 (1). pp. 212-217.
 
Relation http://dx.doi.org/10.1016/j.bbrc.2007.08.005
http://www.eprints.iicb.res.in/1050/