Caffeine and Chlorogenic Acid Combination Attenuate Early-Stage Chemically Induced Colon Carcinogenesis in Mice: Involvement of oncomiR miR-21a-5p

Author(s)

Bartolomeu, Ariane Rocha ; Romualdo, Guilherme Ribeiro ; Lison, Carmen Grinan ; Besharat, Zein Mersini ; Marchal Corrales, Juan Antonio ; Garcia Chaves, Maria Angel ; Barbisan, Luis Fernando

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 11, p. 16-pg., 2022-06-01.

Abstract

Colorectal cancer (CRC) is one of most common cancers worldwide, with high rates of mortality. Epidemiological findings demonstrate that coffee consumption reduces the risk of developing CRC by similar to 13%. In general, in vivo and in vitro findings demonstrate the antiproliferative, antioxidant and proapoptotic effects of brewed coffee or major bioavailable coffee compounds. Thus, it was assessed whether caffeine (CAF) and/or chlorogenic acid (CGA) attenuates the early-stage of chemically induced mouse colon carcinogenesis. Male Swiss mice were submitted to a 1,2-dimethylhydrazine/deoxycholic acid (DMH/DCA)-induced colon carcinogenesis model. These animals received CAF (50 mg/kg), CGA (25 mg/kg) or CAF+CGA (50 + 25 mg/kg) intragastrically for five times/week for ten weeks. CAF+CGA had the most pronounced effects on decreasing epithelial cell proliferation (Ki-67) and increasing apoptosis (cleaved caspase-3) in colonic crypts. This treatment also decreased the levels of proinflammatory cytokines IL-6, IL-17 and TNF-alpha, and downregulated the oncomiR miR-21a-5p in the colon. Accordingly, the analysis of miR-21a-5p targets demonstrated the genes involved in the negative regulation of proliferation and inflammation, and the positive regulation of apoptosis. Ultimately, CAF+CGA attenuated preneoplastic aberrant crypt foci (ACF) development. Our findings suggest that a combination of coffee compounds reduces early-stage colon carcinogenesis by the modulation of miR-21a-5p expression, highlighting the importance of coffee intake to prevent CRC. (AU)

• FAPESP's process: 17/26217-7 - Action of coffee bioactive compounds towards modulation of miRNAs expression during the colon carcinogenesis in vitro and in vivo
• Grantee: Ariane Rocha Bartolomeu
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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: 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