Sulfur‐Coordinated Organoiridium(III) Complexes Exert Breast Anticancer Activity via Inhibition of Wnt/β‐Catenin Signaling. Issue 9 (14th January 2021)

• Record Type: Journal Article
• Authors: Sun, Qi; Wang, Yi; Fu, Qiuxia; Ouyang, Ai; Liu, Shanshan; Wang, Zhongyuan; Su, Zijie; Song, Jiaxing; Zhang, Qianling; Zhang, Pingyu; Lu, Desheng
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 9(2021)
• Page Start: 4841
• Page End: 4848
• Publication Date: 2021-01-14
• Subjects: anti-breast-cancer activity -- bioinorganic chemistry -- metals in medicine -- organoiridium -- Wnt/β-catenin signaling; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202015009
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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/β‐catenin signaling for the first time. Treatment with pbtIrSS and ppyIrSS induces the degradation of LRP6, thereby decreasing the protein levels of DVL2, β‐catenin and activated β‐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/β‐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. Abstract : The effects of sulfur‐coordinated organoiridium(III) complexes were explored with respect to Wnt/β‐catenin signaling, apoptosis, migration, invasion and "stemness" in breast cancer cells for the first time. pbtIrSS exerted appreciable anti‐tumor and anti‐metastatic activities in breast cancer cells by inhibiting Wnt/ β‐catenin signaling and cancer stem cells.