Antimicrobial agent chloroxylenol targets [beta]-catenin-mediated Wnt signaling and exerts anticancer activity in colorectal cancer

Chloroxylenol is the active ingredient of the antibacterial agent Dettol. The anticancer effect and underlying mechanisms of this compound and other common antimicrobial agents have not been clearly elucidated. In the present study, the effects of chloroxylenol, benzalkonium chloride, benzethonium chloride, triclosan and triclocarban on [beta]-catenin-mediated Wnt signaling in colorectal cancer were evaluated using the SuperTOPFlash reporter assay. It was demonstrated that chloroxylenol, but not the other antimicrobial agents tested, inhibited the Wnt/[beta]-catenin signaling pathway by decreasing the nuclear translocation of [beta]-catenin and disrupting [beta]-catenin/T-cell factor 4 complex, which resulted in the downregulation of the Wnt target genes Axin2, Survivin and Leucine-rich G protein-coupled receptor-5. Chloroxylenol effectively inhibited the viability, proliferation, migration and invasion, and sphere formation, and induced apoptosis in HCT116 and SW480 cells. Notably, chloroxylenol attenuated the growth of colorectal cancer in the MC38 cell xenograft model and inhibited organoid formation by the patient-derived cells. Chloroxylenol also demonstrated inhibitory effects on the stemness of colorectal cancer cells. The results of the present study demonstrated that chloroxylenol could exert anti-tumor activities in colorectal cancer by targeting the Wnt/[beta]-catenin signaling pathway, which provided an insight into its therapeutic potential as an anticancer agent. Key words: chloroxylenol, Wnt/[beta]-catenin signaling pathway, [beta]-catenin/T-cell factor 4, colorectal cancer