Institute of Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
National Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Environ Sci Pollut Res Int. 2021 Nov;28(43):60981-60992. doi: 10.1007/s11356-021-14849-8. Epub 2021 Jun 24.
Previous studies have indicated that capsaicin-rich diet and cold weather have shown strong association with tumor incidence. Thus, we investigated the effects of capsaicin and cold exposure in 1,2-dimethylhydrazine (DMH)-induced colorectal cancer as well as the mechanisms underlying capsaicin and cold-induced CRC. Rats were randomly divided into four groups and received cold still water and capsaicin via intragastric gavage until the end of the experiment. The rat's body weight, thymus weight, and food intakes were assessed. Global levels of histone H3K9, H3K18, H3K27, and H4K16 acetylation and histone deacetylase (HDACs) in colon mucosa were assessed by western blot. Expression levels of Toll-like receptors 2 (TLR2) and Toll-like receptors 4 (TLR4) were measured by western blot and reverse-transcriptase quantitative polymerase chain reaction (qPCR). We found that cold and low-dose capsaicin increased tumor numbers and multiplicity, although there were no differences in tumor incidence. Additionally, rat exposure to cold water and capsaicin display further higher levels of histone H3 lysine 9 (H3K9AC), histone H3 lysine 18 (H3K18AC), histone H3 lysine 27 (H3K27AC), and HDACs compared with the DMH and normal rats. In contrast, a considerable decrease of histone H4 lysine 16 (H4K16AC) was detected in the colon mucosa. Cold and low-dose capsaicin exposure groups were also increased TLR2 and TLR4 protein levels and mRNA levels. These results suggest that chronic cold exposure and capsaicin at a low-dose intervention exacerbate ectopic expression of global histone acetylation and TLR level, which are crucial mechanisms responsible for the progression of colorectal cancer in rats.
先前的研究表明，富含辣椒素的饮食和寒冷天气与肿瘤发病率有很强的关联。因此，我们研究了辣椒素和寒冷暴露对 1,2-二甲基肼（DMH）诱导的结直肠癌的影响，以及辣椒素和寒冷诱导 CRC 的潜在机制。大鼠随机分为四组，通过灌胃接受冷水和辣椒素，直至实验结束。评估大鼠体重、胸腺重量和食物摄入量。通过 Western blot 评估结肠黏膜中组蛋白 H3K9、H3K18、H3K27 和 H4K16 乙酰化以及组蛋白去乙酰化酶（HDACs）的整体水平。通过 Western blot 和逆转录定量聚合酶链反应（qPCR）测量 Toll 样受体 2（TLR2）和 Toll 样受体 4（TLR4）的表达水平。我们发现，寒冷和低剂量辣椒素增加了肿瘤数量和多发性，尽管肿瘤发生率没有差异。此外，与 DMH 和正常大鼠相比，暴露于冷水和辣椒素的大鼠显示组蛋白 H3 赖氨酸 9（H3K9AC）、组蛋白 H3 赖氨酸 18（H3K18AC）、组蛋白 H3 赖氨酸 27（H3K27AC）和 HDACs 水平进一步升高。相反，在结肠黏膜中检测到组蛋白 H4 赖氨酸 16（H4K16AC）显著减少。寒冷和低剂量辣椒素暴露组还增加了 TLR2 和 TLR4 蛋白水平和 mRNA 水平。这些结果表明，慢性寒冷暴露和低剂量辣椒素干预加剧了全局组蛋白乙酰化和 TLR 水平的异位表达，这是导致大鼠结直肠癌进展的关键机制。
