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Abstract: Melatonin exerts oncostatic actions and sensitizes tumor cells to chemotherapeutics or radiation. In our study, we investigated the eects of docetaxel, vinorelbine, and radiation on human breast fibroblasts and its modulation by melatonin. Docetaxel or vinorelbine inhibits proliferation and stimulates the dierentiation of breast preadipocytes, by increasing C/EBP and PPAR expression and by downregulating tumor necrosis factor  (TNF), interleukin 6 (IL-6), and IL-11 expression. Radiation inhibits both proliferation and dierentiation through the downregulation of C/EBP and PPAR and by stimulating TNF expression. In addition, docetaxel and radiation decrease aromatase activity and expression by decreasing aromatase promoter II and cyclooxygenases 1 and 2 (COX-1 and COX-2) expression. Melatonin potentiates the stimulatory eect of docetaxel and vinorelbine on dierentiation and their inhibitory eects on aromatase activity and expression, by increasing the stimulatory eect on C/EBP and PPAR expression and the downregulation of antiadipogenic cytokines and COX expression. Melatonin also counteracts the inhibitory eect of radiation on dierentiation of preadipocytes, by increasing C/EBP and PPAR expression and by decreasing TNF expression. Melatonin also potentiates the inhibitory eect exerted by radiation on aromatase activity and expression by increasing the downregulation of promoter II, and COX-1 and COX-2 expression. Our findings suggest that melatonin modulates regulatory eects induced by chemotherapeutic drugs or radiation on preadipocytes, which makes it a promising adjuvant for chemotherapy and radiotherapy sensibilization.

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