Functional compound obtained by enzymatic hydrolysis of Rutin in xenograft model of human colon adenocarcinoma: changes in the ATM/ATR via and protection potential against to oxidative damage DNA in normal tissues.

• Grant number: 15/07981-2
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2016
• End date: December 31, 2018
• Field of knowledge: Health Sciences - Nutrition
• Principal Investigator: Denise Gonçalves Priolli
• Grantee: Denise Gonçalves Priolli
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil
• Associated researchers: Patrícia de Oliveira Carvalho

Abstract

The most commonly used therapy in colorectal cancer, which keeps great importance due to the high frequency and current incidence, is surgical resection associated with neo and/or adjuvant treatment. However, treatment with antineoplastic have potential for inducing mutagenic effects in normal cells. New chemotherapy drugs are available in order to reduce toxicity. Antineoplastic, ideally, would lead to complete tumors remission while provide protection to normal cells damage. Although the flavonoids cellular and molecular mechanisms are unknown in part, they have demonstrated antitumor activity as well as protective effect in normal cells, so it is a potential desirable antitumor agents. Among its possible protective actions are included antioxidant capacity, direct radical scavengers, chelating agents of ions of metals, inactivating carcinogens, while its antitumor activity seems related to modulation of gene expression and DNA repair, hormonal modulator, enzyme inhibitors and apoptosis inducers. It is known that biological effects depend on the chemical structure of naturally occurring flavonoid, such that changes in these compounds generate bioactive molecules. The modification of its structure also influences the efficiency of absorption. The quercetin-3-rutinosídeo can be transformed into quercetin-3-glucoside for breach of rhamnose molecule for the alpha-L-rhamnosidase, resulting in significant increase in its bioavailability. It has already demonstrated its antitumor action. The main objective of this study in vitro models, in vivo and ex vivo, through morphological, molecular and analytical methods is to investigate the functional compound obtained by enzymatic hydrolysis of rutin to a) modify the expression of genes via ATM and oxidative response in colon adenocarcinoma, b) protect from oxidative DNA damage normal tissues (kidney, spleen, liver) in in vivo model of colon adenocarcinoma, c) improve understanding of the ATR/ATM pathway. Therefore it is expected to demonstrate the antitumor activity of functional compound obtained by enzymatic hydrolysis of rutin in colon adenocarcinoma; a protective response in normal target organs (liver, spleen and kidney) and enhance knowledge about the involvement of the compound in the ATM / ATR pathway in adenocarcinoma of the colon. (AU)

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)

NICOLUCCI, CAMILLA; LAPO PAIS, MARIANA; SANTOS, A. C.; RIBEIRO, FABIANA M.; ENCARNACAO, PEDRO M. C. C.; SILVA, ANA L. M.; CASTRO, I. F.; CORREIA, PEDRO M. M.; VELOSO, JOAO F. C. A.; REIS, JULIE; et al. Single Low Dose of Cocaine-Structural Brain Injury Without Metabolic and Behavioral Changes. FRONTIERS IN NEUROSCIENCE, v. 14, JAN 22 2021. (15/07981-2, 17/26010-3)