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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 Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2018
Effective date (End): January 09, 2022
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal Investigator:Luís Fernando Barbisan
Grantee:Ariane Rocha Bartolomeu
Host 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


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)

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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)
AMADEU, SIMONE OLIVEIRA; SARMIENTO-MACHADO, LUIS MANUEL; BARTOLOMEU, ARIANE ROCHA; GARCIA CHAVES, MARIA ANGEL; ROMUALDO, GUILHERME RIBEIRO; DE MOURA, NELCI ANTUNES; BARBISAN, LUIS FERNANDO. Arthrospira (Spirulina) platensis feeding reduces the early stage of chemically induced rat colon carcinogenesis. BRITISH JOURNAL OF NUTRITION, v. N/A, p. 11-pg., . (17/26217-7)
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, . (16/12015-0, 16/14420-0, 17/26217-7)
BARTOLOMEU, ARIANE ROCHA; ROMUALDO, GUILHERME RIBEIRO; LISON, CARMEN GRINAN; BESHARAT, ZEIN MERSINI; MARCHAL CORRALES, JUAN ANTONIO; GARCIA CHAVES, MARIA ANGEL; BARBISAN, LUIS FERNANDO. Caffeine and Chlorogenic Acid Combination Attenuate Early-Stage Chemically Induced Colon Carcinogenesis in Mice: Involvement of oncomiR miR-21a-5p. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 11, p. 16-pg., . (17/26217-7, 16/12015-0, 16/14420-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
BARTOLOMEU, Ariane Rocha. Ação dos compostos bioativos do café durante a carcinogênese de cólon em modelos in vitro e in vivo. 2022. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu Botucatu.

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