文献类型：期刊文献

英文题名：Sulfur-Coordinated Organoiridium(III) Complexes Exert Breast Anticancer Activity via Inhibition of Wnt/β-Catenin Signaling

作者：Sun, Qi[1];Wang, Yi[2,3];Fu, Qiuxia[1];Ouyang, Ai[2];Liu, Shanshan[1];Wang, Zhongyuan[1];Su, Zijie[1];Song, Jiaxing[1];Zhang, Qianling[2];Zhang, Pingyu[2];Lu, Desheng[1]

机构：[1]Shenzhen Univ, Hlth Sci Ctr, Dept Pharmacol, Guangdong Key Lab Genome Stabil & Dis Prevent,Int, Shenzhen 518060, Peoples R China;[2]Shenzhen Univ, Coll Chem & Environm Engn, Shenzhen 518060, Peoples R China;[3]East China Univ Sci & Technol, Sch Chem & Mol Engn, Key Lab Adv Mat MOE, Shanghai 200237, Peoples R China

年份：2021

卷号：60

期号：9

起止页码：4841

外文期刊名：ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

收录：;EI(收录号：20210309783968);WOS:【SCI-EXPANDED(收录号:WOS:000607546000001)】；

基金：This work was supported by the National Nature Science Foundation of China (Grant No. 81802662, 22077085, 21671137 and 31970739), the Nature Science Foundation of Guangdong Province (Grant No. 2017A030310329, 2019A1515011958 and 2020A1515010340), the Shenzhen Peacock Innovation Team Project (Grant KQTD20140630100658078), the Shenzhen Basic Research Program (Grant No. JCYJ20170817094611664, JCYJ20190808153209537 and JCYJ20190808173601655), the Shenzhen Peacock Plan (Grant No.827000186 and 827000183), the SZU medical young scientists program (Grant No. 71201-000001) and the Medical Science and Technology Research Foundation of Guangdong Province (Grant No. A2019475). We are thankful for resources provided by the Instrumental Analysis Center of Shenzhen University.

语种：英文

外文关键词：anti-breast-cancer activity; bioinorganic chemistry; metals in medicine; organoiridium; Wnt/beta-catenin signaling

摘要：The sulfur-coordinated organoiridium(III) complexes pbtIrSS and ppyIrSS, which contain C,N and S,S (dithione) chelating ligands, were found to inhibit breast cancer tumorigenesis and metastasis by targeting Wnt/beta-catenin signaling for the first time. Treatment with pbtIrSS and ppyIrSS induces the degradation of LRP6, thereby decreasing the protein levels of DVL2, beta-catenin and activated beta-catenin, resulting in downregulation of Wnt target genes CD44 and survivin. Additionally, pbtIrSS and ppyIrSS can suppress cell migration and invasion of breast cancer cells. Furthermore, both complexes show the ability to inhibit sphere formation and mediate the stemness properties of breast cancer cells. Importantly, pbtIrSS exerts potent anti-tumor and anti-metastasis effects in mouse xenograft models through the blockage of Wnt/beta-catenin signaling. Taken together, our results indicate that pbtIrSS has great potential to be developed as a breast cancer therapeutic agent with a novel mechanism.