THE ROLE OF ENDOCANNABINOID RECEPTORS IN THE TREATMENT OF PROSTATE CANCER ASSOCIATED WITH HYPERLIPIDIC DIET AND PHYSICAL EXERCISE

• Grant number: 23/16663-0
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2024
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Giovana Rampazzo Teixeira
• Grantee: Giovana Rampazzo Teixeira
• Host Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil
• Associated researchers: Adelino Sanchez Ramos da Silva ; Aldo Eloizo Job ; Gisele Alborghetti Nai ; Ines Cristina Giometti Ceda ; Rafael Jesus Gonçalves Rubira

Abstract

Prostate tumors commonly exhibit pronounced accumulations of saturated lipids and cholesterol due to upregulated lipogenesis and intracellular uptake of circulating lipoproteins. Furthermore, lipid deposits fuel the progression of previously benign lesions into increasingly aggressive and metastatic tumors. To mitigate the spread of lethal tumors, the stimulation of cannabinoid receptors (CB1 and CB2) was recently proposed, which systemically regulate glucose metabolism and lipogenesis in the prostate and its action is still poorly studied. It is known that physical exercise is efficient in modulating the factors that promote the development of prostate cancer, as well as being efficient as an auxiliary therapy in treatment, reducing proliferation and inducing apoptosis. Therefore, it is extremely important to reveal the activation of CB1 and CB2 in prostate cancer associated with a high-fat diet and physical exercise. Therefore, our objective will be to investigate the action of cannabinoids in the treatment of prostate cancer and its lipid regulation associated with a high-fat diet and physical exercise. In the first stage we aimed to evaluate the effects of the administration of agonist cannabinoids and the distinct manipulation of the FAAH enzyme (Knockdown) on lipid content, mitochondrial biogenesis, autophagy and oxidative stress of RWPE-1, PC3, LNCaP and DU145 cells. In stage 2, we will investigate the role of a high-fat diet in modulating prostate cancer in mice and treatments with cannabinoid agonists and physical exercise. The following adaptations resulting from this protocol will be analyzed: functional (physical performance), morphological (histopathology and marking of proteins involved in metabolism and autophagy), biochemical (antioxidant activity), and molecular (lipid content and mitochondrial protein content and autophagy). Thus, understanding the effects of cannabinoid agonists associated with physical exercise, which may be capable of modulating the lipid and protein part of the prostate, acts as a promising hope for mapping pathways responsible for inhibiting cell proliferation and apoptosis, thus providing new possibilities therapeutics and treatment for disorders involving prostate cancer. (AU)