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Effect of papaya dietary fibers on in vivo model of rats with chemically induced Colon Carcinogenesis and on Colon Cancer cell spheroids

Grant number: 19/18794-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2020
Status:Discontinued
Field of knowledge:Agronomical Sciences - Food Science and Technology - Food Science
Principal researcher:Joao Paulo Fabi
Grantee:Janaina Lombello Santos Donadio
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/07914-8 - FoRC - Food Research Center, AP.CEPID
Associated scholarship(s):21/07292-3 - Influence of papaya pectins on host pro-inflammatory cytokine responses using 3D models of human colon mucosa, BE.EP.PD

Abstract

The consumption of dietary fiber (AF) has been related to the decrease in the incidence of Colon Cancer. Fruits, such as papaya, are rich in pectins, which represents the water-soluble fraction of the fruit. Papaya has a very rapid maturation process, with softening of the pulp and modification of the fiber structures. In addition, papaya fibers have been linked to a number of beneficial biological effects (such as decreased cell proliferation) in a structurally dependent manner when studied in two-dimensional (2D) culture using Cancer cells. However, the effects of different fiber structures on more complex experimental models, such as in vivo carcinogenesis model using rats and in 3D culture of human Colon Cancer cells, are not yet known. Thus, the present project aims to evaluate the physiological effects of the consumption of fibers from unripe and ripe papaya in rats with pre-neoplastic colon lesions, as well as to evaluate the effects of fibers from unripe and ripe papaya in co-culture 3D spheroids using Colon Cancer cells (HCT116 and HT29) and human fibroblasts (CCD-18Co). For that aim, rats will be chemically induced to develop pre-neoplastic lesions and will be fed with the unripe and ripe papaya fibers. The metabolization of the fibers and the production of metabolites such as Short Chain Fatty Acids (SCFA) will be evaluated. The pectins of unripe and ripe papayas will be used in the treatments of 3D cellular co-culture and will be evaluated the evolution of the tumor in the 3D model, the cellular viability and the expression of some proteins involved in this process. Thus, it will be possible to analyze whether the structure-dependent effects of fibers remain in two models more complex than only the two-dimensional cell culture. From the health point of view, the results obtained could expand the knowledge of how structural alterations of AF during maturation impact their effects on the development of Colon Cancer. From the technological and commercial point of view, the elucidation of the relation between pectin structure and activity may open a new perspective for the prospection of new supplements and functional foods. (AU)

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