Identification of phenolic compounds in jabuticaba leaves (Myrciaria cauliflora): Phytochemical characterization, investigation of bioactivities and toxicological effects of vescalagin and castalagin ellagitannins in human hepatocarcinoma spheroids

• Grant number: 22/15267-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2023
• Status: Discontinued
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Lusânia Maria Greggi Antunes
• Grantee: Carolina Girotto Pressete
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 24/08830-7 - Identification, phytochemical, functional analyses and bioactivity of phenolic compounds from jabuticabeira (Myrciaria cauliflora) leaves for incorporation into microbeads, BE.EP.PD

Abstract

Cancer is a genetic disease characterized by uncontrolled cell division. Bioactive compounds found in plants, known as phytochemicals, can act as chemopreventive/chemotherapeutic agents in cancer, with more than 20,000 different phytochemicals with potential antitumor effects found in fruits and vegetables. Extracts obtained from seeds and bark of fruit species are increasingly studied for their chemopreventive and antitumor activities. The present work aims to investigate the cytotoxic, genotoxic, antiproliferative and antiangiogenic effects of jabuticaba leaf extract and its isolated ellagitannins vescalagin and castalagin in HepG2 cell line (human cellular hepatocarcinoma) cultivated in a two-dimensional (2D) model and tumor multicellular spheroids (3D). The extract will be obtained from jabuticabeira leaves and its phytochemical characterization and quantification of ellagitannins vescalagin and castalagin found in the extract will be carried out. The evaluated parameters will be cell viability/cytotoxicity/proliferation (LC50, IG50, IC50), antiangiogenic activity, formation of reactive species; clonogenic assay; cell cycle, induction of apoptosis, induction of DNA damage, invasiveness and cell migration. The molecular mechanisms related to the antitumor activity will be investigated by the expression of the genes mTOR, BAX, BCL-2, CASP3, CASP7, CASP9, STAT-3, AKT1, PARP1 and CDKN1A, related to the molecular pathways of induction of apoptosis and cell proliferation and of the VEGF, VEGFR-2, MMP-9, MMP-2 and BFGF genes, related to angiogenesis and cell invasiveness. This research is interdisciplinary with significant knowledge transfer.