RT Journal Article T1 Caffeine and Chlorogenic Acid Combination Attenuate Early-Stage Chemically Induced Colon Carcinogenesis in Mice: Involvement of oncomiR miR-21a-5p. A1 Bartolomeu, Ariane Rocha A1 Romualdo, Guilherme Ribeiro A1 Lison, Carmen Griñan A1 Besharat, Zein Mersini A1 Corrales, Juan Antonio Marchal A1 Garcia Chaves, Maria Angel A1 Barbisan, Luis Fernando K1 caffeine K1 chemically induced colon carcinogenesis K1 chlorogenic acid K1 miRNA expression K1 mice AB 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 ~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-α, 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. PB MDPI AG YR 2022 FD 2022-05-28 LK http://hdl.handle.net/10668/21162 UL http://hdl.handle.net/10668/21162 LA en NO Bartolomeu AR, Romualdo GR, Lisón CG, Besharat ZM, Corrales JAM, Garcia Chaves MÁ, et al. Barbisan LF. Caffeine and Chlorogenic Acid Combination Attenuate Early-Stage Chemically Induced Colon Carcinogenesis in Mice: Involvement of oncomiR miR-21a-5p. Int J Mol Sci. 2022 Jun 4;23(11):6292. DS RISalud RD Apr 9, 2025