Regulation of NLRP3 inflammasome and Caspase-3/4/11 by 2′,4′-dihydroxychalcone contributes to anti-colorectal cancer

作者：Guohui Zhang, Yixin Yao, Zhongyu Zhang, Jianbo Xiao, Hua Yu, Jinmin Zhao, Chun Yao, Yitao Wang, Hua Luo · 发表于：Phytomedicine · 年份：2024 · DOI：10.1016/j.phymed.2024.156194 · 被引用次数：9 · 研究领域：Inflammasome and immune disorders、Toxin Mechanisms and Immunotoxins、Cell death mechanisms and regulation

Chronic inflammation is closely related to the occurrence and progression of many cancers, especially colorectal cancer (CRC), which can be triggered by repeated and sustained induction of colitis in mice. CRC is a typical type of cancer that can be caused by inflammation and NLRP3 inflammasome dysregulation plays a certain role in the pathogenesis of CRC. As an edible Chinese medicine, Abrus cantoniensis Hance (ACH) has both anti-inflammatory and anti-tumor activities. However, most research has focused on inflammation-related diseases, and less research has been done on its active ingredients and targets and its application in CRC. Here, this study deeply explored the target of 2′,4′-DHC and its pharmacological mechanism in anti-colon cancer, and provided a new strategy for its drug development and treatment of colon cancer. The cytotoxicity of ACH's active ingredient in HT29 and CT26 cells was measured by CCK-8, clone formation, apoptosis, and cell cycle assay. The metastasis inhibition of CRC cells was determined by wound-healing assay. Western blotting was used to detect the NLRP3 inflammasome activation, pyroptosis, and apoptosis activation. Finally, the in vivo efficacy of 2′,4′-DHC was verified by establishing CT26 and HT29 tumor transplant models in mice. Here, our study firstly demonstrated that 2′,4′-DHC inhibited the growth of CRC cells mainly by increasing CRC cell death and ameliorating tumor immunosuppressive environment, which is verified by inducing apoptosis...