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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: JOURNAL OF NUTRITIONAL BIOCHEMISTRY; v. 85, NOV 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 16/14420-0 - miRNA expression in Fibrosis-associated Hepatocarcinogenesis: Modulation by Caffeine, Trigonelline and Chlorogenic Acid.
• Grantee: Luís Fernando Barbisan
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/12015-0 - Caffeine, Trigonelline and Chlorogenic Acid: Modulation of miRNA expression in Fibrosis-associated Hepatocarcinogenesis.
• Grantee: Guilherme Ribeiro Romualdo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/16596-0 - Bioactive coffee compounds and their effects on liver fibrosis
• Grantee: Gabriel Bacil Prata
• Support Opportunities: Scholarships in Brazil - Scientific Initiation