Inhibition of hormone-/growth factor-induced rise in cytosolic free calcium ([Ca2+]i) in human prostate cancer and choriocarcinoma cells by melatonin.

Abstract

Melatonin, a pineal gland neurohormone, has been shown to inhibit the proliferation of specific human cancer cells, some of which are derived from reproductive tissues such as the prostate and placenta. In many of these in vitro studies, the signal transduction mechanisms of the anti-proliferative action of melatonin are largely undefined. Given that calcium ion is an important second messenger which plays a pivotal role in the modulation of basic cellular processes such as proliferation, differentiation and apoptosis, the effects of melatonin on cytosolic calcium ([Ca2+]i) levels in human prostate LNCaP and PC-3 cells as well as choriocarcinoma JEG-3 cells were investigated. In addition, the effects of melatonin on changes in [Ca2+]i in LNCaP, PC-3 and JEG-3 cells induced, respectively, by sex steroids, gastrin-releasing peptide (GRP) and insulin-like growth factor I (IGF-I) were also studied. Although melatonin was found to exert no effect on basal [Ca2+]i in LNCaP cells, it reduced, dose-dependently (5 nM to 50 µM), the Ca2+ influx into LNCaP cells induced by 1 µM 17ß-estradiol (E2) or 0.1 µM 5•-dihydrotestosterone (DHT). Interestingly, estrogen and androgen antagonists (tamoxifen and cyproterone acetate) failed to block the Ca2+ influx into LNCaP cells induced by E2 and DHT. Similar to the results obtained in LNCaP cells, melatonin did not affect the basal [Ca2+]i in PC-3 and JEG-3 cells. While the rise in [Ca2+]i induced by 1 nM GRP in PC-3 cells was abrogated by 5 x 10–10M melatonin, IGF-I (10–8M)-induced increase in [Ca2+]i in JEG-3 cells was inhibited by 5 x 10–7 M melatonin. Our data suggest that melatonin may interact with sex steroids, GRP and IGF-I, through changes in intracellular calcium, in the modulation of the proliferation of androgen-sensitive LNCaP prostate cancer cells, androgen-insensitive PC-3 prostate cancer cells and choriocarcinoma JEG-3 cells respectively. The work described in this abstract was partially supported by a research grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKU 7069/ 99M).