Interaction between Vitamin D analogs and anticancer drug (cediranib) in human malignant melanoma cell lines

• Grant number: 18/06042-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: June 01, 2018
• End date: November 02, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Claudia Helena Pellizzon
• Grantee: Fernando Pereira Beserra
• Supervisor: Michal Zmijewski
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: Medical University of Gdańsk (MUG), Poland
• Associated to the scholarship: 14/23247-4 - Evaluation of the cellular and molecular mechanisms of lupeol-based cream on the process of cutaneous wound healing in experimental models of diabetic and nondiabetic rats, BP.DR

Abstract

Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Vitamin D is a lipid soluble steroid hormone with pleiotropic biological properties, including regulation of cell proliferation, differentiation and apoptosis. As to these desirable anticancer actions, 1,25-dihydroxyvitamins D and analogs have been reported to inhibit the proliferation and to induce differentiation of a wide variety of cancer cell types, including human malignant melanoma. We will investigate whether secosteroidal analogs, both classic 1,25(OH)2D3 and its low calcemic analog calcipotriol can enhance the antitumor activity of cediranib in human malignant melanoma cell lines. The results from this study will be supported by cell cycle and apoptosis analyses, proliferation assay, measurement of the mitochondrial transmembrane potentials and mRNA and protein expression. Knockdown of VDR and PDIA3 will be achieved by siRNA and a cross talk between pathways activated by vitamin D analogs and anticancer drug, cediranib will be performed. This project contributes to the development of new alternatives for the treatment of human melanoma. (AU)