The role of melatonin in malignant disease

The review summarizes experimental and preliminary clinical findings relating to the application of melatonin in malignancy to allow a differential discussion concerning its potential therapeutic use in cancer patients. In vivo experiments show that melatonin inhibits chemically induced, as well as spontaneous rodent tumors, but is mostly ineffective in controlling the growth of undifferentiated transplantable tumors. Some human and murine in vitro cancer cell lines are inhibited by physiological concentrations of melatonin, but the majority of the tested cell lines is resistant to melatonin or can be inhibited at pharmacological doses only. In individual cases melatonin was reported to stimulate cell growth. The molecular mechanisms of how melatonin affects the proliferation of cancer cells under in vivo and in vitro conditions are mostly unknown and their elucidation will require further basic research to determine the therapeutic potential of melatonin. From a theoretical point of view substitution therapy with melatonin might be worthwhile since a progressive decline of pineal melatonin secretion is observed parallel to the growth of the primary tumor in breast and prostate cancer. The mechanisms involved in this depression are at present poorly understood but do not appear to be identical among species so that similar results in animal experiments are of limited applicability to humans. First clinical experience with melatonin in the treatment of cancer patients has been confined to adjuvant therapies at advanced and terminal stages of malignancy and have yielded certain encouraging results. It is imperative to verify these preliminary data applying double-blind protocols and future therapeutic trials of melatonin in patients with early-stage malignant disease should be contemplated. Evidence exists that the role of the pineal gland in malignancy may not be confined to melatonin since potent antineoplastic fractions of yet unknown chemical structure have been detected which are capable of inhibiting in vitro cell lines resistant to melatonin.