Lipid modulation by Orlistat and exogenous palmitate association in biomarker prostate cancer

• Grant number: 20/03889-2
• Support Opportunities: Scholarships abroad - Research
• Start date: February 10, 2023
• End date: February 09, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Giovana Rampazzo Teixeira
• Grantee: Giovana Rampazzo Teixeira
• Host Investigator: Artem Pliss
• Host Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil
• Institution abroad: State University of New York, Buffalo State (SUNY), United States

Abstract

Prostate cancer (PCa) metabolism appears to be unique in comparison with other type of solid cancers. Normal prostate cells mainly rely on glucose oxidation to the synthesis and secretion of citrate. Cancer cells show an altered metabolic phenotype characterized by increased glucose levels, glutaminolysis and synthesis of de novo fatty acid (FA), being considered targets for understanding these changes. The link between PCa development and lipid metabolism is well established, with AR and closely involved lipogenic processes involving sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FASN), enzyme acetyl CoA carboxylase (ACC), ATP citrate lyase (ACLY), Stearoyl-CoA Desaturase 1 (SCD1) and carnitine palmitoyltransferase-1 (CPT1). However, increased de novo lipid synthesis, strictly intertwined with deregulation in classical oncogenes and onco suppressors, is an early event of the disease. Characteristic changes in lipogenic phenotypes are expressed in frequent tumors, with an increase in FASN activity. On the other hand, normal, non-tumoral tissues, express little FASN. Lipid synthesis intermediates and FA catabolism also emerged as important players in PCa maintenance. Pharmacological inhibitors of FASN are being evaluated in clinical trials for treatment of cancer, obesity and other diseases. Orlistat is an inhibitor of the FASN, an enzyme strongly linked to tumor progression. By virtue of its ability to inhibit fatty acid synthase, Orlistat halts tumor cell proliferation, induces tumor cell apoptosis, and inhibits the growth of PC-3 tumors in nude mice. In this way, we will verify the lipid accumulation in PCa cell lines, associated with the application of orlistat and exogenous palmitate. (AU)