[Cyanidin-3-O-glucoside inhibits proliferation of colorectal cancer cells by targeting TOPK].

Objective To explore the influence of cyanidin-3-O-glucoside (C3G) on the proliferation of colorectal cancer cells and its mechanism. Methods In vitro binding and in vitro kinase assay were used to detect the binding ability of C3G and T-LAK cell-originated protein kinase (TOPK) and its effect on TOPK activity. Soft AGAR test was used to detect the effect of C3G on the clonal ability of colon cancer cells. The cytotoxicity of C3G was determined by MTS assay. E. coli BL21 was used to express GST-histone H3 fusion protein. The effect of C3G on the clonogenesis of colon cancer cells with silenced TOPK was examined by lentivirus infection. The phosphorylation of histone H3 by C3G in HCT116 cells was determined by Western blotting. A mouse model of xenograft was established to study the phosphorylation level of histone H3 by immunohistochemical staining. Results C3G was directly bound to TOPK in vitro and inhibited TOPK activity. C3G inhibited the proliferation and clone formation of colon cancer cells in a concentration-dependent manner. Silencing TOPK decreased the sensitivity of colon cancer cells to C3G. C3G inhibited the phosphorylation of histone H3 downstream of TOPK in a time- and concentration-dependent manner. In addition, C3G inhibited tumor growth in mice with xenograft tumors from colon cancer tissues of a patient. Conclusion C3G can inhibit colorectal cancer growth by targeting TOPK.