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Melanogenic activity of Platinun (II)Complex with derivates of Hydantoines as a new route of cytotoxicity in melanoma

Grant number: 11/15729-0
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2012
Effective date (End): May 31, 2013
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Silvya Stuchi Maria-Engler
Grantee:Fernanda Branco Filippin
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The metastatic melanoma is resistant to therapies with high recurrence rates, giving the patient a very poor prognosis. The precise cause of therapeutic resistance in melanoma is still unknown and some mechanisms are proposed, including: mechanism of multi-drug resistance (MDR), overexpression of inhibitors of apoptosis, altered gene expression and induction of pathways and cell survival time more recently include the detoxification of drugs by melanosomes (organelles responsible for producing melanin) in a process dependent on the formation of autophagosomes. It is known that the characteristics of melanosomes, including their biogenesis, density and structural integrity, regulate chemoresistance melanoma and that manipulation of the dynamics of melanosomes can be an effective way to improve the therapeutic activity of chemotherapy for the treatment of melanoma. Our goal is to recognize that the platinum II complexes with hydantoin derivatives has an impact on the mechanisms of melanogenesis and thus decreasing the chemoresistance besides elucidating a new route for cytotoxicity in vitro model of human melanoma. The methodology we use methods of molecular and cellular biology as cytotoxicity tests generating dose-response curves, evaluation of this route bay melanogenic pathways with its inhibitor, evaluation of the autophagic mechanism of resistance in this setting and if the modulation of autophagy could contribute to melanogenesis and decreased chemoresistance using new synthetic molecules that combine cisplatin with hydantoin complex whose mechanism of action cause induction of the melanogenic activity.