Effect of melatonin and all-trans retinoic acid on the proliferation and induction of the apoptotic pathway in the culture of human breast cancer cell line MCF-7.

Melatonin in the in vitro conditions inhibits cell growth and proliferation of estrogen sensitive (ER+) cell line MCF-7 in culture. In the present study, during a 48-hour incubation melatonin at a concentration of 10(-5) M inhibited [3H]thymidine incorporation into cancer cells at the level of 69.52% +/- 10.99. Melatonin had no inhibitory effect on the physiological stimulatory action of estradiol. Tamoxifen added to the medium modulated the melatonin action only when the latter was added 24 hours after tamoxifen (46.45% +/- 4.40, p < 0.05). Tretinoin added to the culture caused a statistically significant reduction in [3H]thymidine incorporation into the cancer cells, compared to the melatonin and tretinoin groups, when treatment with retinoid was synergistic (39.05% +/- 5.44, p < 0.05) or sequential (tretinoin and after 24 h melatonin) (39.96% +/- 1.55, p < 0.05). This was confirmed by immunocytochemical investigations, which showed a statistically significant reduction in the percentage of PCNA- and Ki67-positive cells. Apart from the inhibitory effect on MCF-7 cell proliferation retinoids induce the apoptotic pathway in a dose-dependent manner. Melatonin added to the culture enhances this effect, which may indicate the potential for the use of both substances in the treatment of breast cancer in women.