Sulfur‐coordinated organoiridium(III) complexes exert anti‐breast cancer activity via inhibiting Wnt/β‐catenin signaling

The sulfur-coordinated organoiridium(III) complexes pbtIrSS and ppyIrSS , which contain C,N and S,S (dithione) chelating ligands, are found to inhibit breast cancer tumorigenesis and metastasis via targeting Wnt/β-catenin signaling for the first time. Treatment with pbtIrSS and ppyIrSS induce 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 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.