Brazilian berry (Myrciaria jaboticaba) peel extract as an adjuvant therapy to androgen deprivation in castration-resistant Prostate Cancer: studies on apoptosis and tumor neovascularization regulatory mechanisms

• Grant number: 22/09692-1
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2023 - March 31, 2025
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Fabio Montico
• Grantee: Fabio Montico
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Mário Roberto Maróstica Junior ; Valéria Helena Alves Cagnon Quitete

Abstract

Prostate cancer (PCa) is the second most common cancer in men and its progression requires the development of a new vascular network to supply oxygen and nutrients to the tumor. This phenomenon can occur from preexisting vessels, thus defining angiogenesis, or through vessel-independent mechanisms, such as vasculogenic mimicry (VM), which has been registered mainly in aggressive and metastatic tumors. In the prostate, the standard protocol for treating advanced tumor stages is androgen deprivation therapy (ADT) involving the administration of hormonal signaling inhibitors, such as enzalutamide. Despite this, progression to castration-resistant prostate cancer (CRPC), an incurable and lethal stage of the disease, is a common finding in clinical practice. At this stage, tumor cells usually acquire enzalutamide resistance by means of gene regulation promoted by microRNAs (miRNAs), leading to apoptosis evasion and enhanced tumorigenic capacity. Considering this background, developing new adjuvant therapies is a crucial need to slow CRPC progression and to extend patients lifespan. In this scenario, plant-derived bioactive compounds, such as the polyphenols from Brazilian berry (also known as "jabuticaba" / Myrciaria jaboticaba) peel, has emerged as promising alternatives due to their well-known antioxidant and anti- inflammatory properties without any significant side effects. Thus, the aim herewith will be to evaluate the potential of "jabuticaba" peel extract (JPE) as an adjuvant therapy to ADT in CRPC in vitro, as well as along the development of such disease stage in the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) preclinical model. At the end of the study, we expect to unravel the molecular mechanisms involved in PJE actions on essential processes for tumor progression towards androgen-independent stages, such as apoptosis and tumor vascularization. (AU)