Seriniquinone and its derivative LT406 as antimelanoma agents in experimental models

Abstract

Cancer is the second leading cause of death in the world today, making important the development of new drugs and the study of the molecular bases of tumorigenesis. Through bioprospection of secondary metabolites of microorganisms, seriniquinone (SQ) was isolated from a marine bacterium of the genus Serinicoccus. Further studies have shown that SQ regulates the expression of the dermicidin gene (DCD), a protein which function is not understood yet in neoplasia, and induces cell death by autophagy with selectivity for melanoma cells, the most aggressive skin cancer. More recent studies with the synthetic derivative of SQ named LT406, it has been evaluated cytotoxicity, colony formation and cell cycle in melanoma lines with the most recurrent mutations: BRAFV600E and NRAS. With promising results, both substances showed antitumor potential and more studies of the mechanism of action are required. In addition, the present project will also address the treatment of melanoma cells that are resistant to vemurafenib (PLX4032), a drug used today in the clinic where chemoresistance is highly reported. In vitro assays will be performed to evaluate the toxicity and mechanism of action with special emphasis on the participation of the dermicidin protein in the mechanisms of chemoresistance and SQ action. In vivo studies will also be performed through xenographic model. (AU)