Pachymic acid activates TP53INP2/TRAF6/caspase-8 pathway to promote apoptosis in renal cell carcinoma cells

作者全名："Li, Xunjia; He, An; Liu, Chengxuan; Li, Ying; Luo, Yan; Xiong, Weijian; Nian, Weiqi; Zuo, Deyu"

作者地址："[Li, Xunjia; Liu, Chengxuan; Li, Ying; Luo, Yan; Xiong, Weijian] Chongqing Hosp Tradit Chinese Med, Dept Nephrol, Chongqing, Peoples R China; [Li, Xunjia] Chongqing Precis Med Ind Technol Res Inst, Dept Res & Dev, Chongqing 400000, Peoples R China; [He, An] Chongqing Med Univ, Div Cardiol, Affiliated Hosp 1, Chongqing, Peoples R China; [Nian, Weiqi] Chongqing Hosp Tradit Chinese Med, Dept Oncol, Chongqing, Peoples R China; [Zuo, Deyu] Chongqing Tradit Chinese Med Hosp, Dept Rehabil Med, Chongqing, Peoples R China; [Nian, Weiqi] Chongqing Hosp Tradit Chinese Med, Dept Oncol, Panxi Rd 6, Chongqing 400021, Peoples R China; [Zuo, Deyu] Chongqing Hosp Tradit Chinese Med, Dept Rehabil Med, Panxi Rd 6, Chongqing 400021, Peoples R China"

通信作者："Nian, WQ (通讯作者)，Chongqing Hosp Tradit Chinese Med, Dept Oncol, Panxi Rd 6, Chongqing 400021, Peoples R China.; Zuo, DY (通讯作者)，Chongqing Hosp Tradit Chinese Med, Dept Rehabil Med, Panxi Rd 6, Chongqing 400021, Peoples R China."

来源：ENVIRONMENTAL TOXICOLOGY

ESI学科分类：ENVIRONMENT/ECOLOGY

WOS号：WOS:001194548900001

JCR分区：Q1

影响因子：4.5

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：apoptosis; caspase 8; natural products; pachymic acid; renal cell carcinoma; TP53INP2; TRAF6; ubiquitination

摘要："While pachymic acid (PA), a key component of Poria cocos (Schw.), has demonstrated anti-tumor effects in lung, breast, and pancreatic cancers, its impact on renal cell carcinoma (RCC) is unclear. This study evaluated the effect of PA on proliferation, migration, and apoptosis in human renal cancer A498 and ACHN cells as well as in cancer xenograft mice using wound scratch test, Western blotting, and co-immunoprecipitation assays. In a dose- and time-dependent manner, PA exhibited significant inhibition of RCC cell proliferation, migration, and invasion, accompanied by the induction of apoptosis. Additionally, PA upregulated the expression of tumor protein p53-inducible nuclear protein 2 (TP53INP2) and tumor necrosis factor receptor-associated factor 6 (TRAF6), which were downregulated in renal papillary and chromophobe carcinoma, resulting in inhibited tumor growth in mice. PA treatment elevated cleaved-caspase 3 and 8, and PARP levels, and facilitated TP53INP2 and TRAF6 binding to caspase 8, promoting its ubiquitination. Molecular docking revealed interactions between PA and TP53INP2, TRAF6. In summary, PA inhibits RCC development by upregulating TP53INP2 and promoting TRAF6-induced caspase 8 ubiquitination, activating apoptotic pathways."

基金机构：Special Project for Performance Incentive and Guidance of Scientific Research Institutions in Chongqing

基金资助正文：No Statement Availabler No Statement Available