Abstract:
: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 RORalpha. 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 RORalpha receptor, which is expressed in LNCaP cells.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Moretti RM,Montagnani Marelli M,Motta M,Limonta Pdoi
10.1002/1097-0215(20010601)92:5<733::aid-ijc1254>3keywords:
subject
Has Abstractpub_date
2001-06-01 00:00:00pages
733-7issue
5eissn
0020-7136issn
1097-0215pii
10.1002/1097-0215(20010601)92:5<733::AID-IJC1254>3journal_volume
92pub_type
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