Long-lasting inflammation in the intestinal tract renders individuals susceptible to colitisassociated cancer (CAC). The NOD-like receptor protein 3 (NLRP3) inflammasome plays a key role in the progression of inflammatory bowel disease and CAC. Therefore, identifying effective drugs that prevent CAC by targeting NLRP3 inflammasome is of great interest. Here, we aimed to evaluate the anti-inflammatory effect of caffeic acid phenethyl ester (CAPE) on bone marrow-derived macrophages (BMDMs), THP-1 cells, and azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon cancer mouse model. We also investigated the anti-tumor mechanism of CAPE. We found that CAPE decreased NLRP3 inflammasome activation in BMDMs and THP-1 cells and protected mice from colorectal cancer induced by AOM/DSS. CAPE regulated NLRP3 at the posttranscriptional level by inhibiting reactive oxygen species (ROS) production. However, CAPE did not affect NLRP3 or IL-1β transcription, but instead enhanced NLRP3 binding to ubiquitin molecules, promoting NLRP3 ubiquitination, and contributing to the antitumor effect in the AOM/DSS mouse model. Moreover, CAPE suppressed the interaction between NLRP3 and CSN5 but enhanced that between NLRP3 and Cullin1 both in vivo and in vitro. Altogether, our findings demonstrate that CAPE prevents CAC by post-transcriptionally inhibiting NLRP3 inflammasome. Thus, CAPE may be an effective candidate for reducing the risk of CAC in patients with inflammatory bowel disease.

BackgroundThere are few clinical challenges associated with the treatment of colorectal cancer (CRC). Studies have shown that TGF-β plays a crucial role in CRC. Importantly, celastrol, a major components of the root extract of the traditional Chinese herb Tripterygium wilfordii Hook F, has been shown to inhibit the growth, adhesion, and metastasis of human CRC cells through the inhibition of TGF-β1/Smad signaling.Materials and methodsReal-time PCR and Western blot tests were proceeded to present TGF-β1, TGF-β receptor type I (TGFβRI), TGF-β receptor type II (TGFβRII), Smad2/3, p-Smad2/3, Smad4, and glyceraldehyde-3-phosphate dehydrogenase expression in human colon cancer cell samples.ResultsOur results indicated that celastrol can reduce the expression levels of TGF-β1, TGFβRI, and TGFβRII in HCT116 and SW620 cells. Furthermore, celastrol could also prevent the increase in Smad4 and p-Smad2/3 in HCT116 and SW620 cells.ConclusionCelastrol could inhibit tumor growth through TGF-β1/Smad signaling and might be a promising therapeutic component against CRC.

Non-small cell lung cancer (NSCLC) is one of the most common malignancies. Studies have shown that engulfment and cell motility 3 (ELMO3) is highly expressed in NSCLC and can be used as a novel biomarker, but its underlying mechanism remains to be explored. The aim of this study was to investigate the mechanism by which ELMO3 may be down-regulated by COX-2 inhibitors to inhibit NSCLC. NSCLC tissue and adjacent normal lung tissue from 24 patients were used to detect the mRNA and protein expression of ELMO3, COX-2, and other related proteins by Western blot, RT-PCR, and Immunohistochemical analysis. Lewis Lung carcinoma (LLC) cells were used to investigate the effects and the mechanism of siELMO3 and COX-2 inhibitor. C57BL/6 mice inoculated with LLC cells by subcutaneous (s.c.) injection were used to detect the in vivo effects of cox-2 inhibitor. The expression of ELMO3 and cyclooxygenase-2 (COX-2) in human NSCLC tissues was significantly increased compared with that in the adjacent normal tissues. ELMO3 exhibited a positive correlation with COX-2 expression. Moreover, knockdown of ELMO3 suppressed the epithelial-mesenchymal transition (EMT), adhesion, and metastasis of Lewis lung carcinoma (LLC) cells. Importantly, Parecoxib, a selective inhibitor of COX-2, significantly reduced the expression of ELMO3 and EMT in LLC cells and LLC-bearing mice. Furthermore, it could inhibit the growth, adhesion and metastasis of LLC cells in vitro . Our results demonstrate that down regulation of ELMO3 suppressed growth and metastasis of lung cancer by inhibiting EMT. Parecoxib could reduce ELMO3 expression and suppress growth and metastasis of lung cancer, which might be a useful chemotherapeutic agent for inhibiting metastasis and recurrence of NSCLC.

Pyroptosis is a novel form of programmed cell death (PCD), which is characterized by DNA fragmentation, chromatin condensation, cell swelling and leakage of cell contents. The process of pyroptosis is performed by certain inflammasome and executor gasdermin family member. Previous researches have manifested that pyroptosis is closely related to human diseases (such as inflammatory diseases) and malignant tumors, while the regulation mechanism of pyroptosis is not yet clear. Non-coding RNA (ncRNA) such as microRNA (miRNA), long non-coding RNA (lncRNA) and circular RNA (circRNA) have been widely identified in the genome of eukaryotes and played a paramount role in the development of cell function and fate after transcription. Accumulating evidences support the importance of ncRNA biology in the hallmarks of pyroptosis. However, the associations between ncRNA and pyroptosis are rarely reviewed. In this review, we are trying to summarize the regulation and function of ncRNA in cell pyroptosis, which provides a new research direction and ideas for the study of pyroptosis in different diseases.

A rapid and high sensitive ultra high performance liquid chromatography with tandem mass spectrometry method for the simultaneous determination of notoginsenoside R1 and ginsenoside Re in rat plasma was developed. The analytes and internal standard, digoxin, were extracted from rat plasma via protein precipitation with methanol and separated on an Phenomenex Gemini C18 column within 2 min. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique, operating in multiple reaction monitoring and positive ion mode. The precursor to product ion transitions monitored for notoginsenoside R1, ginsenoside Re, and internal standard were m/z 955.5→775.5, 969.6→789.1, and 803.6→283.1, respectively. The assay was validated with linear range of 1.9-380 ng/mL for notoginsenoside R1 and 0.5-100 ng/mL for ginsenoside Re. The intra- and interday precisions (RSD%) were within 8.96% for each analyte. The absolute recoveries were greater than 93% for R1 and 96% for Re. Each analyte was stable during all sample storage, preparation, and analytic procedures. The method was successfully applied to a pharmacokinetic study of Xuesaitong dispersible tablets in eight rats.