THE ROLE OF CANNABINOID RECEPTORS AS AN ALTERNATIVE THERAPY FOR THE TREATMENT OF PROSTATIC CANCER ASSOCIATED WITH A HIGH-FAT DIET AND AEROBIC PHYSICAL EXERCISE

• Grant number: 23/17712-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2024
• End date: October 31, 2028
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Giovana Rampazzo Teixeira
• Grantee: Maria Eduarda de Almeida Tavares
• Host Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil

Abstract

Prostate cancer (CaP) is the leading cause of death in men from cancer. The increase in the activity of proliferative pathways, with a concomitant reduction in apoptotic pathways and loss of tumor suppressors, leads to tumor development and progression. The lipid bioavailability promoted by obesity induced by a high-fat diet (HFD) leads to metabolic reprogramming, providing increased energy for cell proliferation, and also associated with a worse prognosis. The stimulation of cannabinoid receptors (CB1 and CB2) systemically regulates the metabolism of glucose, lipids, and lipogenesis, in the prostate its action is still little studied, however, it is known that it reduces pathways associated with the progression of PCa, however, its action associated with HFD, is still unknown. Physical exercise is efficient in reducing the factors that promote the development of PCa, as well as being efficient as an auxiliary therapy in treatment, reducing proliferation and inducing apoptosis. However, its action on CB1 and CB2 in HFD-associated prostate cancer is still unknown. Therefore, our objective will be to characterize the action of exogenous cannabinoids in the treatment of prostate cancer and their lipid regulation in prostate cancer cells. To verify the action of exogenous cannabinoids in the treatment of prostatic adenocarcinoma associated with a high-fat diet and aerobic physical exercise and the possible protective action of exogenous cannabinoids in the treatment of prostate cancer. Prostatic cancer cell culture lines will be used: RWPE-1, PC3, LNCaP and DU145 cells and C57BL/6 mice and TRAMP mice, divided into 6 groups (n=16): C57BL/6 control animals; Animals C57BL/6 HFD+WIN 55.212-2; Animals C57BL/6 HFD+WIN 55.212-2 and submitted to the aerobic physical training protocol; TRAMP control animals; Animals TRAMP HFD+WIN 55.212-2; TRAMP HFD+ WIN 55.212-2 animals and submitted to the aerobic physical training protocol. The high-fat diet will consist of 45 Kcal % fat, for 13 weeks. The aerobic physical training protocol will consist of running on an ergometric treadmill adapted for mice, 60% of the incremental load test, for 5 days a week, for 8 weeks. The animals will be euthanized, the prostate will be collected and processed for histopathological analysis, Western Blotting and RT-PCR and the blood will be used for biochemical plasma analysis. Prostate cancer cells will be used for lipidomics analysis.