THE VALIDITY OF MELATONIN AS AN ONCOSTATIC AGENT

The validity of melatonin as a prominent, naturally occurring oncostat ic agent is examined in terms of its putative oncostatic mechanism of action, the correlation between melatonin levels and neoplastic activi ty, and the outcome of therapeutically administered melatonin in clini cal trials. Melatonin's mechanism of action is summarized in a brief a nalysis of its actions at the cellular level, its antioxidative functi ons, and its indirect immunostimulatory effects. The difficulties of i nterpreting melatonin levels as a diagnostic or prognostic aid in canc er is illustrated by referral to breast cancer, the most frequently st udied neoplasm in trials regarding melatonin. Trials in which melatoni n was used therapeutically are reviewed, i.e., early studies using mel atonin alone, trials of melatonin in combination with interleukin-2, a nd controlled studies comparing routine therapy to therapy in combinat ion with melatonin. A table compiling the studies in which melatonin w as used in the treatment of cancer in humans is presented according to the type of neoplasm. Melatonin's suitability in combination chemothe rapy, where it augments the anticancer effect of other chemotherapeuti c drugs while decreasing some of the toxic side effects, is described. Based on the evidence derived from melatonin's antiproliferative, ant ioxidative, and immunostimulatory mechanisms of action, from its abnor mal levels in cancer patients and from clinical trials in which melato nin was administered, it is concluded that melatonin could indeed be c onsidered a physiological anticancer substance. Further well-controlle d trials should, however, be performed in order to find the link betwe en its observed effects and the underlying mechanisms of action and to define its significance as a therapeutic oncostatic agent.