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

Abstract

Previous studies have indicated that capsaicin-rich diet and cold weather have showed strong association with tumor incidence. Thus, we investigated the effects of capsaicin and cold exposure in 1,2-dimethylhydrazine-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, H4K16 acetylation and, histone deacetylase (HDACs) in colon mucosa were assessed by western blot. Expression levels of Tolllike receptors 2 (TLR2) and Toll-like receptors 4 (TLR4) were measured by western-blot and reversetranscriptase quantitative polymerase chain reaction (qPCR). We found that cold and low-does capsaicin increased tumor numbers and multiplicity, although there were no differences in tumor incidence.Additionally, rat exposure of 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 group were also increased TLR2 and 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 TLR level, which are crucial mechanisms responsible for the progression of colorectal cancer in rat.

Antioxidant and Anticancer Potentials of the Olive and Sesame Mixture against Dimethylhydrazine-Induced Colorectal Cancer in Wistar Rats

“…The DMH exerts its effects by damaging the mucus, methylating the tissue, and forming free radicals [ 50 ]. In addition, it is shown that oral antioxidants can decline the effects and lesions caused by DMH [ 51 , 52 ].…”

Toll‐like receptors in health and disease

“…It was discovered that TLR2 expression was much elevated in CRC patients, and this had an impact on patient survival. TLR2 stimulation increased the migration, invasion, and proliferation of CRC cells 184–187 . Furthermore, the gut flora contribute significantly to the advancement of CRC, and Fusobacterium nucleatum enhances the development of CRC by upregulating the expression of inflammatory mediators via TLR2 signaling 188,189 .…”

“…The expression of TLRs is elevated in multiple cancer types, such as those affecting the liver, intestinal tract, and oral cavity. These receptors are essential for the development and spread of malignant tumors as well as the prognosis of cancer 170–173,184–187,202,231–236,319,320 . TLRs promote carcinogenesis by inducing different cells to release proinflammatory cytokines and antiapoptotic factors, recruiting immune cells, and promoting cell proliferation in TME, thereby creating a tumor‐friendly environment.…”

“…TLR2 stimulation increased the migration, invasion, and proliferation of CRC cells. 184 , 185 , 186 , 187 Furthermore, the gut flora contribute significantly to the advancement of CRC, and Fusobacterium nucleatum enhances the development of CRC by upregulating the expression of inflammatory mediators via TLR2 signaling. 188 , 189 In order to promote CRC, Pseudomonas fluorescens interacts with TLR2/4 on host cells to cause the generation of ROS, boosts cholesterol biosynthesis by controlling sterol‐regulatory element binding protein 2 (SREBP2), and activates prooncogenic genes and pathways.…”

“…These receptors are essential for the development and spread of malignant tumors as well as the prognosis of cancer. 170 , 171 , 172 , 173 , 184 , 185 , 186 , 187 , 202 , 231 , 232 , 233 , 234 , 235 , 236 , 319 , 320 TLRs promote carcinogenesis by inducing different cells to release proinflammatory cytokines and antiapoptotic factors, recruiting immune cells, and promoting cell proliferation in TME, thereby creating a tumor‐friendly environment. Their therapeutic use is expected as well, considering the important function played by the molecules in the TLR pathway in the innate immune system; however, this is probably because immune cells and/or cancer cells activate distinct TLRs and downstream signaling cascades; alternatively, because of the temporal sequence of TLR activation in cancer cells or immune cells, studies on the role of TLR antagonists and agonists in inflammation and even cancer have been controversial (Table 2 ).…”