Signaling pathways of melanoma regression: focus on melatonin

Abstract

Faithful to its inherent aggressive, melanomas are remarkably resistant to all forms of cancer therapies. The combination of chemotherapy with biomolecules such as IL-2 and IFN-alpha does not appear to be an effective management. However, clinical trials are underway to evaluate new therapeutic strategies. In this context, melatonin (MLT) has been shown to be an excellent adjunct to conventional chemotherapy associated with IL-2 immunotherapy. MLT not only reduces the growth of melanoma, but also significantly suppresses the toxicity of chemotherapy drugs and enhances its cytotoxicity anticancer. Although the oncostatic property of MLT is well established, its mechanism of action is not known. Supported by our previous results which show that the MLT decreases cell proliferation of two strains of human melanoma (SK-Mel-19 and SK-Mel-147) and given the different susceptibility of these strains to MLT treatment, we intend to define the pathways of intracellular signaling activated or inhibited by MLT on a panel of metastatic melanoma and normal cells. The group of Dr. Maria S. Soengas has excellence in melanoma research focusing on processes involved or associated with cell death by apoptosis, and so was chosen for this project. The desired results may open new paths of research for a new therapeutic approach for melanoma. (AU)