Food Bioactive compounds and the potential promotion of antitumoral response in colon cancer: An in vitro and in vivo analysis on their influence on immunotherapy and chemotherapy

• Grant number: 24/09284-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2024
• End date: July 31, 2026
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Guilherme Ribeiro Romualdo
• Grantee: Giullia Cavicchioli Barbosa
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 22/06082-8 - Multimodel Drug Screening Platform (MDSP): preclinical and molecular insights for Colon and Liver Cancer management, AP.GR

Abstract

The Colorectal Carcinoma (CCR) has a high incidence and mortality worldwide, along with a poor prognosis. Most affected patients, generally in advanced stages, resort to low-responsive systemic therapies. Modulation of the tumor microenvironment is also overlooked in antineoplastic therapies. Prominent epidemiological studies highlight that vegetable consumption may reduce the risk for CCR. These foods are reservoirs of many bioactive compounds (BCs) that have already demonstrated antiproliferative, pro-apoptotic, and anti-inflammatory effects in preclinical studies, such as chlorogenic acid (CGA), phenethyl isothiocyanate (PEITC), and ²-cryptoxanthin (BCX). Due to the need to increase the efficacy of current therapies, we will evaluate whether the administration - alone or in combination - of PEITC isothiocyanate, ACG polyphenol, and BCX carotenoid, abundant in vegetables, promotes improvement in the antitumor response of 5-fluorouracil+Bevacizumab therapy in in vivo and in vitro models of CCR. To this end, we will establish co-culture models of CCR tumor cells (HCT-116) and fibroblasts (CCD-18Co). The co-cultures will be treated with BCs - alone or in combination - and with the respective therapies for 24 or 48 hours. We will evaluate viability (MTT), cytotoxicity (LDH), motility (scratch assay), and invasion (transwell assay). Next, the Combination Index (CI) will be calculated, and combinations with additive/synergistic results will be selected for the in vivo study. BALB/c nude mice will be subjected to xenograft tumor models by implanting tumors formed from HCT-116/CCD-18Co cells. The animals will be treated with the selected BCs and respective therapies, and immunohistochemistry of Ki-67, caspase-3, CD31, and VEGF will be evaluated, as well as the main tumorigenic and tumor microenvironment pathways at the transcriptomic level (NanoString) in the tumors.