Action of coffee bioactive compounds towards modulation of miRNAs expression during the colon carcinogenesis in vitro and in vivo

• Grant number: 17/26217-7
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2018
• Effective date (End): November 09, 2021
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Luís Fernando Barbisan
• Grantee: Ariane Rocha Bartolomeu
• Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated scholarship(s): 19/21413-8 - Effects of bioactive coffee compounds on human colorectal cancer stem cell-like in spheroids (3D) culture, BE.EP.DR

Abstract

Colorectal Cancer (CRC) is one of most common Cancer in worldwide within high mortality rates. Studies have been demonstrating several biological activities of coffee and it compounds, such as, antiproliferative and antitumoral effects. Therefore, our project goals to evaluate the effects of coffee bioactive compounds (chlorogenic acid, caffeine and trigonelline) alone or combined treatments towards: (A) cytotoxicity and antiproliferative action against colon tumor cell lines; (B) colon carcinogenesis; (C) the profile of miRNA global expression; (D) modulation of target genes miRNA differentially expressed at colon. In vitro and in vivo models will submitted to exposure of coffee bioactive compounds (chlorogenic acid, caffeine and trigonelline) treatments. The cytotoxicity essay will carried under colorectal adenocarcinoma cell lines (Caco-2 HCT-116 and HT-29) through mitochondrial reductase activity assay, lactate dehydrogenase release, wound healing assay, flow cytometric analysis and molecular expression of main genes related to CRC. The in vivo model stablished is the chemical induction of CRC (male Balb-C mice) from DMH/ADC (dimethylhidrazine/deoxycholic bile acid) method. Histopathological and immunohistochemical analysis will proceed on colon samples. Part of frozen samples will utilized in global miRNA expression (nCounter miRNA Expression Assay). The identification of differentially miRNA expression will followed by bioinformatics prediction of microRNAs target genes. Finally, the predicted genes list will allow the evaluation the mRNAs targets expression by RT-qPCR. (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)

ROMUALDO, GUILHERME RIBEIRO; ROCHA, ARIANE BARTOLOMEU; VINKEN, MATHIEU; COGLIATI, BRUNO; MORENO, FERNANDO SALVADOR; GARCIA CHAVES, MARIA ANGEL; BARBISAN, LUIS FERNANDO. Drinking for protection? Epidemiological and experimental evidence on the beneficial effects of coffee or major coffee compounds against gastrointestinal and liver carcinogenesis. Food Research International, v. 123, p. 567-589, SEP 2019. Web of Science Citations: 1.