Chelerythrine chloride inhibits the progression of colorectal cancer by targeting cancer-associated fibroblasts through intervention with WNT10B/beta-catenin and TGF beta 2/Smad2/3 axis

作者全名："Liang, Dan; Liu, Lu; Zheng, Qiao; Zhao, Maoyuan; Zhang, Gang; Tang, Shiyun; Tang, Jianyuan; Chen, Nianzhi"

作者地址："[Liang, Dan; Zheng, Qiao; Zhao, Maoyuan; Zhang, Gang; Tang, Jianyuan] Hosp Chengdu Univ Tradit Chinese Med, TCM Regulating Metab Dis Key Lab Sichuan Prov, Chengdu, Peoples R China; [Liu, Lu] Chengdu Univ Tradit Chinese Med, Coll Pharm, Chengdu, Peoples R China; [Tang, Shiyun] Hosp Chengdu Univ Tradit Chinese Med, Chengdu, Peoples R China; [Chen, Nianzhi] Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing, Peoples R China"

通信作者："Tang, JY (通讯作者)，Hosp Chengdu Univ Tradit Chinese Med, TCM Regulating Metab Dis Key Lab Sichuan Prov, Chengdu, Peoples R China.; Tang, SY (通讯作者)，Hosp Chengdu Univ Tradit Chinese Med, Chengdu, Peoples R China.; Chen, NZ (通讯作者)，Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing, Peoples R China."

来源：PHYTOTHERAPY RESEARCH

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001023393400001

JCR分区：Q1

影响因子：6.1

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：cancer-associated fibroblasts; chelerythrine chloride; colorectal cancer; TGF-beta 2/Smad2/3; WNT10B/beta-catenin

摘要："Chelerythrine chloride (CHE) is a benzodiazepine alkaloid derived from natural herbs with significant anti-tumor and anti-inflammatory activities. However, the exact role and underlying mechanisms of CHE in colorectal cancer (CRC) remain unclear. Therefore, this study is aimed to investigate the influence of CHE on the progression of CRC. Cell Counting Kit-8 assay (CCK-8), transwell, apoptosis rate, cell cycle distribution, reactive oxygen species (ROS), and colony formation determined the antiproliferative activity of CHE in CRC cell lines. Transcriptome sequencing and western blot were used to explore the mechanism. Finally, H&E staining, Ki67, TUNEL, and immunofluorescence were conducted to verify the anti-CRC activity and potential mechanisms of CHE in vivo. CHE had a prominent inhibitory effect on the proliferation of CRC cells. CHE induces G1 and S phase arrest and induces cell apoptosis by ROS accumulation. Cancer-associated fibroblasts (CAFs) play a key role in CRC metastasis. Then, this study found that CHE regulates WNT10B/beta-catenin and TGF beta 2/Smad2/3 axis, thereby decreasing the expression of alpha-SMA, which is a maker of CAFs. Taken together, CHE is a candidate drug and a potent compound for metastatic CRC, which can intervene CAFs in a dual pathway to effectively inhibit the invasion and migration of cancer cells, which can provide a new choice for future clinical treatment."

基金机构：Chengdu University of Traditional Chinese Medicine [QJRC2022008]; Department of Science and Technology of Sichuan Province [2021ZYD0107]; National Natural Science Foundation of China [82074397]

基金资助正文："Chengdu University of Traditional Chinese Medicine, Grant/Award Number: QJRC2022008; Department of Science and Technology of Sichuan Province, Grant/Award Number: 2021ZYD0107; National Natural Science Foundation of China, Grant/Award Number: 82074397"