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Growth‐inhibitory activity of melatonin on human androgen‐independent DU 145 prostate cancer cells
Author(s) -
Marelli M. Montagnani,
Limonta P.,
Maggi R.,
Motta M.,
Moretti R.M.
Publication year - 2000
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/1097-0045(20001101)45:3<238::aid-pros6>3.0.co;2-w
Subject(s) - melatonin , endocrinology , medicine , biology , melatonin receptor , intracellular , cell cycle , receptor , cell growth , pineal gland , cancer cell , cancer , microbiology and biotechnology , biochemistry
BACKGROUND The pineal hormone melatonin has been shown to exert a direct oncostatic activity on neoplastic cells, particularly from breast cancer. In the present study, we evaluated the effects of melatonin on the proliferation and on the cell cycle distribution of human androgen‐independent DU 145 prostate cancer cells. Experiments were also performed to gain insights into the possible mechanism of action of the hormone. METHODS The effects of melatonin on DU 145 cell proliferation was analyzed by counting the cells by hemocytometer at the end of treatment. The effects of the pineal hormone on cell cycle distribution were evaluated by FACS analysis. RT‐PCR studies were performed to detect Mel 1a and Mel 1b expression in DU 145 cells. The cellular localization of 125 I‐melatonin binding sites was investigated by radioreceptor assay. A commercially available binding‐protein assay kit was utilized to evaluate intracellular cAMP levels. RESULTS Melatonin, in physiological doses, significantly inhibited DU 145 cell proliferation and induced cell cycle withdrawal by accumulating cells in G0/G1 phase. The mRNA for Mel 1a receptors was found to be expressed in DU 145 cells; however, by radioreceptor assay, no binding sites for 125 I‐melatonin could be detected in membrane preparations, suggesting that, in these cells, the level of translation of this mRNA is too low to possibly mediate the antiproliferative action of the hormone. In agreement with this hypothesis, melatonin did not affect forskolin‐induced intracellular cAMP accumulation. Binding sites for 125 I‐melatonin were found in nuclear extracts of DU 145 cells. CONCLUSIONS Melatonin exerts a direct oncostatic activity on human androgen‐independent prostate cancer cells, by affecting cell cycle progression. This activity seems to be mediated by nuclear, but not by membrane, receptors. Prostate 45:238–244, 2000. © 2000 Wiley‐Liss, Inc.