Quercetin-induced pyroptosis in colon cancer through NEK7-mediated NLRP3 inflammasome-GSDMD signaling pathway activation

作者全名："Feng, Shi-Han; Zhao, Bin; Zhan, Xue; Li, Rong-Heng; Yang, Qian; Wang, Shu-Mei; Li, Ao"

作者地址："[Feng, Shi-Han; Zhao, Bin; Li, Ao] Chongqing Med Univ, Yong Chuan Hosp, Dept Tradit Chinese Med, Chongqing 402160, Peoples R China; [Zhan, Xue; Yang, Qian; Wang, Shu-Mei] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing 400016, Peoples R China; [Li, Rong-Heng] Chongqing Med Univ, Affiliated Hosp 1, Dept Integrated Tradit Chinese & Western Med, Chongqing 400042, Peoples R China; [Wang, Shu-Mei] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, 1 Med Coll Rd, Chongqing 400016, Peoples R China; [Li, Ao] Chongqing Med Univ, Yong Chuan Hosp, Dept Tradit Chinese Med, 439 Xuan Hua Rd, Chongqing 402160, Peoples R China"

通信作者："Wang, SM (通讯作者)，Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, 1 Med Coll Rd, Chongqing 400016, Peoples R China.; Li, A (通讯作者)，Chongqing Med Univ, Yong Chuan Hosp, Dept Tradit Chinese Med, 439 Xuan Hua Rd, Chongqing 402160, Peoples R China."

来源：AMERICAN JOURNAL OF CANCER RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001195687900004

JCR分区：Q2

影响因子：3.6

年份：2024

卷号：14

期号：3

开始页：934

结束页：958

文献类型：Article

关键词：Colon cancer; quercetin; pyroptosis; NEK7; NLRP3 inflammasome; GSDMD

摘要："Pyroptosis, a gasdermin-mediated lytic cell death, is a new hotspot topic in cancer research, and induction of tumor pyroptosis has emerged as a new target in cancer management. Quercetin (Que), a natural substance, demonstrates promising anticancer action. However, further information is required to fully comprehend the function and mechanism of Que in pyroptosis in colon cancer. This study revealed the underlying mechanism of Queinduced pyroptosis in colon cancer in vitro and in vivo. Que inhibited colon cancer cell growth through gasdermin D (GSDMD)-mediated pyroptosis. Depletion of GSDMD, rather than gasdermin E (GSDME), reversed the cytotoxic effects of Que on colon cancer cells. Que treatment upregulated NIMA-related kinase 7 (NEK7) protein expression, thus facilitating the assembly of the NLRP3 inflammasome and cleavage of GSDMD. NEK7 silencing resulted in colon cancer cell growth in vitro and in vivo. Mechanistically, NEK7 depression restrained the activation of the NLRP3 inflammasome-GSDMD pathway, thus attenuating pyroptosis triggered by Que in colon cancer cells. Furthermore, lower NEK7 and NLRP3 expression levels indicated colon cancer progression. Our results unveiled a novel pattern of anti-colon cancer activity of Que, and activation of NEK7-mediated pyroptosis is potentially a promising therapeutic target for colon cancer, which provides novel experimental proof for the clinical application of Que."

基金机构：National Natural Science Foundation of China [81704033]; Xinglin program of Chongqing TCM/TCM-integrated Key discipline - Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases [2021-ZDXK-DB04]

基金资助正文：This work was supported by the National Natural Science Foundation of China (No. 81704033) and Xinglin program of Chongqing TCM/TCM-integrated Key discipline (No. 2021-ZDXK-DB04) granted by Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases.