Irradiated riboflavin in human melanoma: responsiveness of different cell lines and development of pharmaceutical formulation for topical use

• Grant number: 15/01138-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2015
• End date: February 28, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Enzymology
• Principal Investigator: Carmen Veríssima Ferreira
• Grantee: Marina Pereira Dias
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The incidence of skin cancer is increasing worldwide, and the melanoma is the one with the highest mortality rate, due to its metastatic potential, and worst prognosis. Thus, the search and the development of new effective drugs with antitumor, antiproliferative and antimetastatic properties that improve the therapeutic efficiency, are needed. Our group has been added in the literature relevant findings about the antitumor potential of riboflavin and its photoproducts, since we demonstrated in various hematopoietic and solid tumor models that this vitamin of the B complex induces cancer cells death by apoptosis. Furthermore, in the context of molecular action, we demonstrated that irradiated riboflavin is able to decrease the expression of several proteins involved with survival, proliferation and migration of tumor cells. It is noteworthy that some of those proteins are considered as tumor aggressiveness markers. More recently, another important finding was the observation that the irradiated riboflavin was also able to reduce the metastatic potential of murine melanoma cells to the lungs, in vivo. According to these findings and taking into account that: a) riboflavin and its photoproducts are found naturally in human metabolism; b) the dose of effectiveness as antitumoral in vitro and in vivo did not show toxicity to humans; c) riboflavin is already approved for clinical use in other pathologies; d) irradiated riboflavin also shows a cytotoxic effect on human melanoma cell lines (SKMEL-2 and SKMEL-28); in the present project the general goals are: to analyze the responsiveness of human melanoma cell lines, including a vemurafenibe resistant one, towards irradiated riboflavin treatment and to develop a pharmaceutical formulation, containing riboflavin and their photoproducts, for topical use. Therefore, this project will bring out as main contribution, an indicative of the specificity of the formulation action in melanoma, with different levels of aggressiveness and/or gene mutations RAF, p53, p16, RAS e BCL2.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

DIAS, Marina Pereira. Development of pharmaceutical formulation for topical administration: responsiveness of human melanoma cell lines. 2017. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.