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Oncostatic activity of a thiazolidinedione derivative on human androgen-dependent prostate cancer cells

✍ Scribed by Roberta M. Moretti; Marina Montagnani Marelli; Marcella Motta; Patrizia Limonta

Publisher: John Wiley and Sons
Year: 2001
Tongue: French
Weight: 115 KB
Volume: 92
Category: Article
ISSN: 0020-7136
DOI: 10.1002/1097-0215(20010601)92:5<733::aid-ijc1254>3.0.co;2-l

No coin nor oath required. For personal study only.

✦ Synopsis

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 ROR␣. Since response elements for this receptor are present in the promoter region of cell cyclerelated 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 androgendependent 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 ROR␣ receptor, which is expressed in LNCaP cells.

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