The combination of coffee compounds attenuates early fibrosis-associated hepatocarcinogenesis in mice: involvement of miRNA profile modulation

Autor(es)

Romualdo, Guilherme Ribeiro ^[1] ; Prata, Gabriel Bacil ^[2] ; da Silva, Tereza Cristina ^[3] ; Evangelista, Adriane Feijo ^[4] ; Reis, Rui Manuel ^{[4, 5, 6]} ; Vinken, Mathieu ^[7] ; Moreno, Fernando Salvador ^[8] ; Cogliati, Bruno ^[3] ; Barbisan, Luis Fernando ^[2]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Botucatu Med Sch, Dept Pathol, Botucatu, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Biosci Inst, Dept Struct & Funct Biol, Prof Dr Antonio Celso Wagner Zanin 250, BR-18618689 Botucatu, SP - Brazil

^[3] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, Sao Paulo, SP - Brazil

^[4] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos, SP - Brazil

^[5] 3Bs PT Govt Associate Lab, Braga - Portugal

^[6] Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, Braga - Portugal

^[7] Vrije Univ Brussel, Fac Med & Pharm, Dept Vitro Toxicol & Dermatocosmetol, Brussels - Belgium

^[8] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Food & Expt Nutr, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NUTRITIONAL BIOCHEMISTRY; v. 85, NOV 2020.
• Citações Web of Science: 0

Resumo

Aberrant microRNA expression implicates on hepatocellular carcinoma (HCC) development. Conversely, coffee consumption reduces by similar to 40% the risk for fibrosis/cirrhosis and HCC, while decaffeinated coffee does not. It is currently unknown whether these protective effects are related to caffeine (CAF), or to its combination with other common and/or highly bioavailable coffee compounds, such as trigonelline (TRI) and chlorogenic add (CGA). We evaluated whether CAF individually or combined with TRI and/or CGA alleviates fibrosis-associated hepatocardnogenesis, examining the involvement of miRNA profile modulation. Then, male C3H/HeJ mice were submitted to a diethyl nitrosami ne/carbon tetrachloride-induced model. Animals received CAF (50 mg/kg), CAI-TRI (50 and 25 mg/kg), CAF-CGA (50 and 25 mg/kg) or CAF+TRI+CGA (50, 25 and 25 mg/kg), intragastrically, 5x/week, for 10 weeks. Only CAF-TRI+CGA combination reduced the incidence, number and proliferation (Ki-67) of hepatocellular preneoplastic foci while enhanced apoptosis (cleaved caspase-3) in adjacent parenchyma. CAF-i-TRI+CGA treatment also decreased hepatic oxidative stress and enhanced the antioxidant Nrf2 axis. CAF-i-TRI+CGA had the most pronounced effects on decreasing hepatic pro-inflammatory IL-17 and NF kappa B, contributing to reduce CD68-positive macrophage number, stellate cell activation, and collagen deposition. In agreement, CAF+TRI CGA upregulated tumor suppressors miR-144-3p, miR-376a-3p and antilibrotic miR-15b-5p, frequently deregulated in human HCC.CAF+TRI+CGA reduced the hepatic protein levels of pro-proliferative EGFR (miR-144-3p target), antiapoptotic Bd-2 family members (miR-15b-5p targets), and the number of PCNA (miR-376a-3p target) positive hepatocytes in preneoplastic foci. Our results suggest that the combination of most common and highly bioavailable coffee compounds, rather than CAF individually, attenuates fibrosis-associated hepatocardnogenesis by modulating miRNA expression profile. (C) 2020 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 16/14420-0 - Expressão de miRNAs na Hepatocarcinogênese associada à Fibrose: modulação pela Cafeína, Trigonelina e Ácido Clorogênico
• Beneficiário: Luís Fernando Barbisan
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/12015-0 - Cafeína, Trigonelina e Ácido Clorogênico: Modulação da expressão de miRNAs na Hepatocarcinogênese associada à Fibrose.
• Beneficiário: Guilherme Ribeiro Romualdo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/16596-0 - Compostos bioativos do café e suas implicações sobre o processo de fibrose hepática
• Beneficiário: Gabriel Bacil Prata
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica