Indole-3-Carbinol Promotes Apoptosis and Inhibits the Metastasis of Esophageal Squamous Cell Carcinoma by Downregulating the Wnt/β-Catenin Signaling Pathway

The incidence and mortality rates of esophageal squamous cell carcinoma (ESCC) have been significantly increasing in China. Indole-3-carbinol (I3C), a naturally occurring component in cruciferous vegetables, is an effective cancer therapy. Yet, its effect and action mechanism in ESCC are still not fully understood. This study explored the role of I3C in ESCC in vitro and in vivo by focusing on the Wnt/beta-catenin signaling pathway. MTT and flow cytometry were used to assess cell viability and apoptosis in EC18 and TE1 cells, while wound healing and transwell assays were used to investigate cell migration and invasion in vitro. Expression of beta-catenin, c-myc, and cyclin D1 was determined by Western blot; LiCl (an agonist of the canonical Wnt signaling that inhibits GSK3 beta activity) was used to assess the role of I3C on the Wnt/beta-catenin signaling pathway. For in vivo experiments, nude BALB/c mice bearing EC18 xenografts were treated with I3C and/or LiCl. I3C promoted ESCC apoptosis and inhibited cell migration and invasion by downregulating beta-catenin, c-myc, and cyclin D1 in vitro and decreased the tumor growth in vivo; this process was reversed by LiCl treatment. In summary, I3C inhibits ESCC malignant behavior by suppressing the Wnt/beta-catenin signaling pathway, thus deeming it a promising drug for ESCC treatment.