JABOTICABA PEEL EXTRACT ASSOCIATED WITH ANDROGENIC ABLATION (ENZALUTAMIDE AND PHYSICAL CASTRATION) IN PROSTATE ADENOCARCINOMA: CELL AND MOLECULAR RESPONSE IN VITRO AND IN VIVO

Abstract

Prostate cancer (PCa) is the second leading cause of cancer death among men. Approximately patients 30% show recurrence of the disease after treatment, who initially responds to androgen deprivation therapy (ADT), and may progress to a therapy resistance PCa, turning into castration-resistance prostate cancer (CRPC). Several therapies are being developed in order to delay or prevent the disease progression such as co-therapy between synthetic drugs and natural compounds. Among the drugs, the Enzalutamide is highlighted, which is a second-generation antiandrogen drug, which is a non-steroidal antagonist that competitively binds to the androgen receptor (AR), inducing apoptosis and inhibiting the proliferation of CRPC cells. Among the natural compounds, the phenolic compounds derived from jaboticaba are being studied, which is a Brazilian fruit with the greatest source of flavonoids of the anthocyanin class, which have antioxidant and anti-proliferative activities. Thus, the objective of the present project will be to characterize the cellular and molecular response, focusing on apoptosis, cell survival and proliferation in PCa, against androgen ablation (Enzalutamide and physical castration) and the jaboticaba peel extract (JPE) administration both in vitro and in vivo. For this, in vitro, the 22Rv1 cell lineage will be analyzed against androgen ablation and JPE administration, through analyzes of cell survival, cell migration and invasion, Western Blotting, cell death (apoptosis or necrosis) and gene expression (quantitative RT-PCR). In vivo, the dorsolateral lobe of transgenic adenocarcinoma of the mouse prostate (TRAMP) will be evaluated against androgen ablation and JPE administration, through morphological, immunohistochemical, Western Blotting and gene expression (quantitative RT-PCR) analyses. Furthermore, based on target genes for apoptosis and AR pathways, it is intend to bioinformatically identify possible miRNAs of interest and verify if there is alteration with androgen ablation and JPE administration, analyzing the expression profile of these miRNAs in the 22Rv1 cell lineage, as well as in the prostate tissue and blood plasma of the TRAMP model.