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.

Highlights

  • Colorectal cancer (CRC) has been recognized as a multi-factorial malignant disorder and remains its status as the most common cause of cancer-related death in men and women (Siegel, Miller, & Jemal, 2019)

  • Cold and low-dose capsaicin exposure group were increased Tolllike receptors 2 (TLR2) and Toll-like receptors 4 (TLR4) proteins levels and mRNA levels. These results suggest that chronic cold exposure and capsaicin at a low-does intervention exacerbate ectopic expression of global histone acetylation and Toll-like receptors (TLRs) level, which are crucial mechanisms responsible for the progression of colorectal cancer in rat

  • Our findings demonstrated that cold exposure and low-does capsaicin administration aggravates the ectopic expression of histone acetylation level and histone-modifying enzymes through the structure of chromatin, making rats-induced by DMH more susceptible to CRC

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Summary

Introduction

Colorectal cancer (CRC) has been recognized as a multi-factorial malignant disorder and remains its status as the most common cause of cancer-related death in men and women (Siegel, Miller, & Jemal, 2019). Colon cancer is caused by complex interactions of the immune system with non-modifiable (eg, genetic and epigenetic alterations) and modifiable (eg, environmental, diet and lifestyle) risk factors (Grazioso, Brandt, & Djouder, 2019; Lao & Grady, 2011). The fact that known high penetrance gene and epigenetic alterations that are related to colorectal cancer risk explain fewer than 5% of the observed case, suggested that environmental factors including diet, alcohol consumption, and ambient environment play a pivotal role in risk (Lichtenstein et al, 2000). Epigenetic modifications have been implicated in the regulation of gene expression, without affecting the DNA sequence (Strahl BD, 2000) Among these modifications, histone acetylation on lysine residues is the most common histone modifications. Much less known regarding the mechanism underlying the putative effect of potential cold and capsaicin exposure contribution on colon carcinoma in rat models

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