Tumor neovascularization in castration-resistant prostate cancer: influence of treatment with Brazilian berry peel extract (Myrciaria jaboticaba) in vivo and in vitro

• Grant number: 23/07294-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2024
• End date: July 31, 2025
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Fabio Montico
• Grantee: Jaqueline de Souza Gianchetto
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Prostate cancer (PCa) is the second most common type in men and its growth and progression require expansion of the local vascular network. Although angiogenesis has been classically studied as the main mechanism of tumor neovascularization, it is currently known that neoplastic cells can acquire the oxygen and nutrients necessary for their survival through alternative routes, such as vasculogenic mimicry (VM). This process consists in the formation of tubular structures similar to blood vessels by the tumor cells themselves, which acquire endothelial characteristics through a specific modality of epithelial-mesenchymal transition (EMT), thus favoring their dissemination and metastasis development. Androgen ablation therapy (ADT) is the recommended approach for the treatment of metastatic PCa and includes the administration of androgen receptor (AR) antagonists, such as enzalutamide. Despite the efficacy initially attributed to this drug, recent studies have reported that tumor cells are capable of acquiring resistance to long-term treatment, culminating in castration-resistant CaP (CRPC), which is responsible for the majority of morbidity and mortality rates associated with the disease. Thus, looking for adjuvant therapies that can delay the development of CRPC without resulting in significant side effects is an urgent need. In this scenario, the use of fractions derived from plant species is a promising alternative, given their high content of bioactive compounds from different classes with proven health benefits. Indeed, previous studies by our research group have already shown the antioxidant, anti-inflammatory and anti-obesogenic effects of jabuticaba peel extract (Myrciaria jaboticaba) (ECJ), as well as its chemopreventive potential against the development of proliferative lesions in the prostatic microenvironment associated with senescence. Considering this, the study herein intends to expand these investigations to the context of PCa, aiming to evaluate the mechanisms of tumor neovascularization, such as angiogenesis and VM, upon ECJ administration associated with androgen ablation, both in vitro and in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) preclinical model. Thus, through in vivo experiments, we expect to verify whether the tumor vascular network can be modulated by the ECJ, thus delaying and/or preventing the progression of CPRC. In addition, in vitro assays may provide evidence on molecular mechanisms of action of the extract and its effects on migration, invasion and ability to form blood vessels or vascular channels by endothelial and tumor cells, respectively.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MONTICO, F.; SOUZA GIANCHETTO, J.; SCHIEVANO, F. R.; FELIX DA SILVA, P.; RABELO SANTOS, F.; LOPES LEMOS, I.; MAROSTICA JUNIOR, M. R.; ALVES CAGNON, V. H.. Effects of Brazilian berry (Myrciaria jaboticaba) peel extract in castration-resistant prostate cancer (CRPC): lobe-specific histopathological responses in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and in vitro evaluation of human tumour cell lines. Virchows Archiv, v. 485, p. 1-pg., 2024-09-01. (22/10794-3, 23/07294-1, 22/09692-1)