膳食可可抑制结肠炎相关癌症:IL-6/STAT3通路的关键作用

Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL-6/STAT3 pathway.

作者信息

Saadatdoust Zeinab, Pandurangan Ashok Kumar, Ananda Sadagopan Suresh Kumar, Mohd Esa Norhaizan, Ismail Amin, Mustafa Mohd Rais

机构信息

Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.

Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

出版信息

J Nutr Biochem. 2015 Dec;26(12):1547-58. doi: 10.1016/j.jnutbio.2015.07.024. Epub 2015 Aug 10.

Abstract

Patients with inflammatory bowel disease (IBD) are at increased risk for developing ulcerative colitis-associated colorectal cancer (CRC). The interleukin-6 (IL-6)/signal transducer and activator of transcription (STAT)-3 signaling regulates survival and proliferation of intestinal epithelial cells and play an important role in the pathogenesis of IBD and CRC. Cocoa is enriched with polyphenols that known to possess antioxidant, anti-inflammatory and antitumor activities. Here, we explored the antitumor effects and mechanisms of cocoa diet on colitis-associated cancer (CAC) using the azoxymethane/dextran sulfate sodium model, with a particular focus on whether cocoa exerts its anticancer effect through the IL-6/STAT3 pathway. We found that cocoa significantly decreased the tumor incidence and size in CAC-induced mice. In addition to inhibiting proliferation of tumor epithelial cells, cocoa suppressed colonic IL-6 expression and subsequently activation of STAT3. Thus, our findings demonstrated that cocoa diet suppresses CAC tumorigenesis, and its antitumor effect is partly mediated by limiting IL-6/STAT3 activation. In addition, cocoa induces apoptosis by increased the expressions of Bax and caspase 3 and decreased Bcl-xl. Thus, we conclude that cocoa may be a potential agent in the prevention and treatment of CAC.

摘要

炎症性肠病(IBD)患者患溃疡性结肠炎相关结直肠癌(CRC)的风险增加。白细胞介素-6(IL-6)/信号转导和转录激活因子(STAT)-3信号通路调节肠道上皮细胞的存活和增殖,在IBD和CRC的发病机制中起重要作用。可可富含多酚,已知多酚具有抗氧化、抗炎和抗肿瘤活性。在此,我们使用氧化偶氮甲烷/葡聚糖硫酸钠模型探讨了可可饮食对结肠炎相关癌症(CAC)的抗肿瘤作用及其机制,特别关注可可是否通过IL-6/STAT3途径发挥其抗癌作用。我们发现可可显著降低了CAC诱导小鼠的肿瘤发生率和肿瘤大小。除了抑制肿瘤上皮细胞的增殖外,可可还抑制结肠IL-6表达并随后抑制STAT3的激活。因此,我们的研究结果表明,可可饮食可抑制CAC的肿瘤发生,其抗肿瘤作用部分是通过限制IL-6/STAT3激活介导的。此外,可可通过增加Bax和caspase 3的表达以及降低Bcl-xl的表达来诱导细胞凋亡。因此,我们得出结论,可可可能是预防和治疗CAC的潜在药物。

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