Oncostatic actions of melatonin

Abstract

In the past few years, extensive interest has been aroused among the research community and the public on the potential of melatonin in the treatment of human diseases on which the current treatment options available are far from satisfactory. A distinct advantage of melatonin is its relative lack of adverse side effects, as demonstrated in animal and human studies, in comparison with many existing conventional drugs or pharmacological agents in development. The majority of findings in the scientific literature support a direct oncostatic action of melatonin on different types of cancer cells particularly by its anti-proliferative effect, despite occasional inconsistent or controversial results. Given that in many of these studies, the signalling mechanisms of melatonin responsible and the in vivo relevance of the in vitro observations to humans are still undefined, we have attempted to delineate the signalling mechanisms of melatonin on the modulation of cell proliferation of human choriocarcinoma and prostate cancer cells. Of note, melatonin was found to inhibit human choriocarcinoma Jar cell proliferation by delaying the transition of the cancer cells from G1 phase to S phase of the cell cycle and such anti-proliferative action of melatonin is likely to be mediated, in part, via MT2 receptors. Importantly, by demonstrating the expression of mt1 melatonin receptor in both LNCaP prostate cancer cells and human prostate cancer tissues from newly-diagnosed patients who have not received prior hormonal therapy and are presumably responsive to anti-androgen therapy, we have established the validity of using the androgen-sensitive LNCaP human prostate cancer cell line as a relevant cellular model for studying the effect of melatonin on androgen-responsive human prostate cancer. Furthermore, our data support the involvement of mt1 receptor and attenuated sex steroidinduced Ca2+ influx in mediating the direct anti-proliferative actions of melatonin on LNCaP cells. The available results suggest that melatonin is an attractive candidate molecule for future research and development as an anti-choriocarcinoma and anti-prostate cancer agent. 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)]