Effect of 3-bromopyruvate in melanoma cells resistant to vemurafenib

• Grant number: 19/14189-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2019
• End date: July 31, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Céline Marques Pinheiro
• Grantee: Patrik da Silva Vital
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
• Associated research grant: 15/25351-6 - MCT1 as a target and response mediator in melanoma therapy, AP.JP

Abstract

The major part of the solid tumors reprograms its energetic metabolism, depending for the most part on the glycolytic pathway for energy obtention, even in the presence of oxygen - a phenomenon known as the Warburg effect. In this context, the monocarboxylates transporters (MCTs), specifically the MCT1 and MCT2 isoforms, perform an essential role, contributing to the continuous flux of glucose, as well as to the pH regulation. Recently, the MCT1 was identified as the principal determinant for the sensibility to the 3-bromopyruvate (3-BP), one of the most promising inhibitors of glycolytic metabolism. In recent years, melanoma patients management has evolved thanks to the best understanding in regards to melanoma molecular heterogeneity; BRAF mutations are associated with an increase in mortality risk, and they are an important factor for therapeutic decisions. Of note, BRAF mutations stimulate the Warburg effect. In this Master Degree project, the potential of 3-BP as an antineoplastic agent for melanomas resistant to vemurafenib will be evaluated. To this end, the effect of the treatment with 3-BP, alone or combined with vemurafenib, under cellular characteristics which include metabolism, viability, proliferation, apoptosis, migration, invasion and colony formation will be tested in melanoma cells resistant to vemurafenib. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VITAL, PATRIK DA SILVA; BONATELLI, MURILO; DIAS, MARINA PEREIRA; DE SALIS, LARISSA VEDOVATO VILELA; PINTO, MARIANA TOMAZINI; BALTAZAR, FATIMA; MARIA-ENGLER, SILVYA STUCHI; PINHEIRO, CELINE. 3-Bromopyruvate Suppresses the Malignant Phenotype of Vemurafenib-Resistant Melanoma Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 24, p. 17-pg., 2022-12-01. (15/25351-6, 19/07502-8, 19/14189-4, 16/13021-4, 16/10821-0, 17/12620-4)