Department of Pathology, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil.
Department of Structural and Functional Biology, Biosciences Institute, São Paulo State University (UNESP), Botucatu 18618-689, SP, Brazil.
Int J Mol Sci. 2022 Jun 4;23(11):6292. doi: 10.3390/ijms23116292.
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.
结直肠癌（CRC）是全球最常见的癌症之一，死亡率很高。流行病学研究结果表明，咖啡的摄入可使 CRC 的发病风险降低约 13%。一般来说，体内和体外的研究结果都表明，煮咖啡或主要可利用的咖啡化合物具有抗增殖、抗氧化和促凋亡作用。因此，研究人员评估了咖啡因（CAF）和/或绿原酸（CGA）是否能减轻化学诱导的小鼠结肠癌变的早期阶段。雄性瑞士小鼠被置于 1,2-二甲基肼/去氧胆酸（DMH/DCA）诱导的结肠癌变模型中。这些动物每周接受 5 次胃内 CAF（50mg/kg）、CGA（25mg/kg）或 CAF+CGA（50+25mg/kg）治疗，共 10 周。CAF+CGA 对降低结肠隐窝上皮细胞增殖（Ki-67）和增加细胞凋亡（cleaved caspase-3）的作用最明显。这种治疗还降低了促炎细胞因子 IL-6、IL-17 和 TNF-α 的水平，并下调了结肠中的致癌 miRNA miR-21a-5p。因此，miR-21a-5p 靶基因的分析表明，这些基因参与增殖和炎症的负调控以及细胞凋亡的正调控。最终，CAF+CGA 减轻了癌前异常隐窝病灶（ACF）的发展。研究结果表明，咖啡化合物的组合通过调节 miR-21a-5p 的表达来减轻结肠癌变的早期阶段，这突显了摄入咖啡预防 CRC 的重要性。
