Aim: 

Melatonin is able to inhibit the aromatase, one of the key enzymes in the local synthesis of estrogens from androgenic precursors in human breast cancer cells. However, the adipose tissue adjacent to the tumor seems to account for most aromatase in breast tumors. Tumor cells secrete factors that inhibit the differentiation of surrounding adipose fibroblasts to mature adipocytes and stimulate aromatase activity and expression in the undifferentiated fibroblasts. Thus, large numbers of estrogen-producing cells are maintained proximal to malignant cells. The aim of this work was to study the effects of melatonin on aromatase in 3T3-L1 cells, a murine fibroblast cell line that can be differentiated into adipocytes.

Methods: 

Triglyceride accumulation was quantitated by the Oil Red method and the aromatase activity by the tritiated water release assay.

Results: 

Melatonin treatment of 3T3-L1 cells during the preadipocyte differentiation enhances the deposits of lipid droplets, an indicator of adipogenic differentiation. The presence of melatonin during the adipose differentiation also induces a 50% reduction in the aromatase activity of the cells. In 3T3-L1 cells completely differentiated into adipocytes melatonin also stimulated the accumulation of triglicerides and inhibited the aromatase activity.

Conclusion: 

Melatonin stimulated the differentiation to adipocyte and adipogenesis and decreased the aromatase activity of 3T3-L1 cells. Thus, we could speculate that melatonin in human breast tumors could also stimulate the differentiation of fibroblast to mature adipocytes and reduce the aromatase activity of the fibroblasts and adipocytes, thus reducing the number of estrogen-producing cells proximal to malignant cells.

Supported by the Spanish MCYT (SAF2007-60659 and 62762).