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Effect of cold exposure and capsaicin on the expression of histone acetylation and Toll-like receptors in 1,2-dimethylhydrazine-induced colon carcinogenesis

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Abstract

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.

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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81673944).

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Jingchun Qin and Huixuan Li wrote the first draft of the manuscript. Bin Wen designed the study. Jingchun Qin, Huixuan Li, and Weitao Yu conducted the experiment and analyzed the data. Li Wei contributed to review and edit the paper. Bin Wen revised the manuscript. All the authors have read and agreed to the published version of the manuscript.

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Correspondence to Bin Wen.

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This study was approved by the institution’s Ethics Review Board (S2017037).

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The authors declare no competing interests.

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Responsible Editor: Ludek Blaha

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Qin, J., Li, H., Yu, W. et al. Effect of cold exposure and capsaicin on the expression of histone acetylation and Toll-like receptors in 1,2-dimethylhydrazine-induced colon carcinogenesis. Environ Sci Pollut Res 28, 60981–60992 (2021). https://doi.org/10.1007/s11356-021-14849-8

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  • DOI: https://doi.org/10.1007/s11356-021-14849-8

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