Effects of melatonin on cancer: studies on MCF-7 human breast cancer cells in culture.

There is some evidence to suggest that the pineal gland influences neoplastic growth. Either crude or partially-purified pineal extracts have been used to treat malignant neoplasms in humans. More compelling evidence indicates that the pineal hormone melatonin, in addition to its well known antireproductive effects, may also exert oncostatic effects particularly in animal models of human breast cancer. However, it is not clear whether melatonin inhibits mammary cancer growth via an indirect neuroendocrine mechanism or via an action directly on the cancer cells themselves. Studies are described in which physiological concentrations of melatonin are shown to have marked inhibitory effects directly on MCF-7 human breast cancer cell growth in culture. Supra- or subphysiological levels of melatonin are completely ineffective in retarding breast cancer cell proliferation. Precursors and metabolites of melatonin such as serotonin, N-acetylserotonin and 6-hydroxymelatonin do not inhibit MCF-7 cell growth. Similarly, neither 5-methoxytryptophol nor 5-methoxytryptamine, regarded by some to be putative pineal hormones, exhibit antimitogenic properties. Melatonin completely blocks the estradiol-induced stimulation of MCF-7 cell proliferation. In defined, serum-free medium, melatonin loses its antimitogenic capabilities unless cells are also simultaneously exposed to either estradiol or prolactin. Therefore, the antiproliferative effect of melatonin may be dependent on the presence of serum and a complex interaction with hormones such as estradiol and/or prolactin.