Ethiadin Induces Apoptosis and Suppresses Growth of MCF-7 Breast Cancer Cells by Regulating the Phosphorylation of Glycogen Synthase Kinase 3 Beta (GSK3beta).

Abstract

Glycogen synthase kinase 3 beta (GSK3β) has emerged as a therapeutic target for breast cancer. As inhibitors of GSK-3β, 1,2,4-thiadiazole-3,5-dione (TDZD) family members have been reported as potential candidates for cancer treatment. In this study, the anticancer effects of ethiadin (ETD-174), one of the chemical synthesis compounds of TDZD, were investigated in MCF-7 human breast cancer cells. MCF-7 cells incubated with different doses of ETD-174 for different time periods. CCK-8 assays were carried out to test the effect of ETD-174 on the proliferation of MCF-7 cells. The occurrence of apoptosis was detected by Hoechst 33258 staining and flow cytometry. ETD-174 on cell migration and colony formation were examined by wound healing experiments and soft agar assays. Relative protein expressions were conducted with immunoblot assay. ETD-174 demonstrated a higher degree of cytotoxicity in MCF-7 cells. Topical morphological changes of apoptotic body formation after ETD-174 treatment were observed. Meanwhile, apoptosis was elicited by ETD-174. Also, ETD-174 could inhibit the migration and clonality of MCF-7 cells. After the treatment with ETD-174, the level of phosphorylation of GSK3β^Ser9 in MCF-7 cells increased significantly, and the enzymatic activity of GSK3β decreased. ETD-174 is likely to have an effective suppressor role in breast cancer, suggesting that pharmacological inhibition of GSK3β as a novel treatment modality for breast cancer should warrant further investigation.