Pharmacological action of high doses of melatonin on B16 murine melanoma cells depends on cell number at time of exposure.

Melatonin has been reported to possess growth inhibitory action at certain physiological doses in cancer cell lines in vitro and oncostatic action under in vivo conditions. In an attempt to achieve a pharmacologically effective anticancer action of melatonin, dose-response studies with high concentrations of melatonin (10(-6) M, 10(-5) M, 10(-4) M and 10(-3) M) were conducted in the B16 murine melanoma cell line using three different numbers of exposed cells. A range of effects, including stimulatory, oncostatic and oncocidal action, were studied 3 days after exposure to melatonin. In order to standardize the results, the concentration of melatonin per cell was calculated from the amount of melatonin added to the culture, and compared with the growth patterns of the cells. Melatonin had a mild stimulatory effect on cell proliferation at the lower end of the dose spectrum and an oncostatic influence at intermediate concentrations, while the higher concentrations per cell demonstrated clear lethal (oncocidal) action. It is suggested that by using a pharmacologically appropriate dosage regimen, melatonin could be useful in the treatment of responsive cancers. Furthermore, calculation of the concentration of melatonin per cell is important in understanding the true pharmacological potential of melatonin.