Hormonal interactions in human prostate tumor LNCaP cells

Melatonin, the hormone secreted by the pineal gland at night, has recently been found to attenuate growth and viability of benign human prostate epith elial cells. Estradiol suppressed these responses by effecting a protein ki nase C mediated inactivation of melatonin receptors. In the present study, the effects of melatonin on growth and viability of the human androgen-sens itive prostatic tumor cell line-LNCaP and the influence of estradiol on the se responses were explored. Melatonin inhibited H-3-thymidine incorporation into LNCaP cells at physiol ogical concentrations. This response decayed within 24 h. The inactivation of the response slowed down in the presence of the protein kinase C inhibit or GF-109203X. Estradiol also inhibited H-3-thymidine incorporation and its effects were additive to those of melatonin. Suppression of DNA content wa s observed in cells treated for 2 days with melatonin (0.1 nM); this suppre ssion was maintained for longer periods in the presence than in the absence of estradiol. In addition, estradiol and melatonin slightly and additively decreased cell viability. These results demonstrate for the first time a direct interaction of melato nin with androgen-sensitive prostate tumor cells leading to attenuation of cell growth. They also show that unlike in benign prostate epithelial cells , estrogen attenuates LNCaP cell growth and supports rather than inactivate s melatonin's action. (C) 1999 Elsevier Science Ltd. All rights reserved.