Influence of papaya pectins on host pro-inflammatory cytokine responses using 3D models of human colon mucosa

• Grant number: 21/07292-3
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 12, 2021
• End date: November 11, 2022
• Field of knowledge: Agronomical Sciences - Food Science and Technology - Food Science
• Principal Investigator: Joao Paulo Fabi
• Grantee: Janaina Lombello Santos Donadio
• Supervisor: Rosangela Mezghanni
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Maryland, Baltimore (UMB), United States
• Associated to the scholarship: 19/18794-0 - Effect of papaya dietary fibers on in vivo model of rats with chemically induced Colon Carcinogenesis and on Colon Cancer cell spheroids, BP.PD

Abstract

Colorectal cancer is a major health problem worldwide. The intake of dietary fiber has been associated to a decrease of colon cancer, especially the intake of soluble fibers, such as pectins. Papaya fibers have been linked to several anti-cancer and anti-inflammatory activities in 2D models, including the induction of apoptosis, cell cycle arrest, and regulation of expression of toll-like receptors. These receptors are essential for the innate immune response that recognizes several molecules shared by pathogens, causing the increase in the expression of pro- and anti-inflammatory cytokines. However, the biological effects of these pectins on more relevant and complex models, such as organoids, have not been studied yet. Therefore, this project aims to evaluate the effect of pectins from papaya on the expression of inflammatory cytokines using two 3D-organoid models: one is a bioengineered multicellular model and the other is an organoid-delivered colonic monolayer. Pectins from ripe and unripe papayas and modified citrus pectin (MCP) will be used to treat the organoids on both models. The expression of inflammatory cytokines will be done by ELISA. The organoids before and after treatments will be submitted to histological staining and immunoassays such as immunofluorescence and immunohistochemistry. (AU)