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Oncostatic activity of a thiazolidinedione derivative on human androgen‐dependent prostate cancer cells
Author(s) -
Moretti Roberta M.,
Montagnani Marelli Marina,
Motta Marcella,
Limonta Patrizia
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20010601)92:5<733::aid-ijc1254>3.0.co;2-l
Subject(s) - lncap , cell cycle , cell growth , cancer research , biology , prostate cancer , androgen receptor , cancer cell , cyclin a , microbiology and biotechnology , cyclin , endocrinology , cell , medicine , cancer , biochemistry , genetics
Thiazolidinedione derivatives with potent antiarthritic activity, such as CGP 52608, have been suggested to exert their biological effects through the activation of the orphan nuclear receptor RORα. Since response elements for this receptor are present in the promoter region of cell cycle‐related genes ( i.e. , p21 WAF1/CIP1 and cyclin A), we reasoned that CGP 52608 might affect cell proliferation, cell cycle progression and the expression of cell cycle‐related genes. This hypothesis has been verified in the human androgen‐dependent prostate cancer cell line LNCaP. We found that the treatment of LNCaP cells with CGP 52608 brings about a significant and dose‐dependent decrease of cell proliferation. Thiazolidinedione affected cell cycle distribution, inducing an accumulation of the cells in the G0/G1 phase and a decrease in the S phase. This effect was accompanied by an increased expression of the cyclin‐dependent kinase inhibitor p21 WAF1/CIP1 and a decreased expression of cyclin A. These data indicate that, in human androgen‐dependent LNCaP prostate cancer cells, the thiazolidinedione derivative CGP 52608 exerts a strong cytostatic activity, by reducing cell proliferation and by affecting cell cycle distribution through the modulation of the expression of cell cycle‐related genes. These biological actions of CGP 52608 might be mediated by the activation of the orphan nuclear RORα receptor, which is expressed in LNCaP cells. © 2001 Wiley‐Liss, Inc.