Scutellarin Protects against Human Colorectal Cancer in vitro by Down Regulation of Hedgehog Signaling Pathway Activity

Background and Objective: It is well known that hedgehog signaling pathway plays a critical role in embryonic development, tissue patterning and carcinogenesis. Scutellarin, a bioactive component in Scutellaria barbata D. Don, is efficacious to various cancers with elusive mechanism to be defined. The objective of the present study was to examine the effect of scutellarin on human colorectal cancer and elaborate the underlying mechanism via hedgehog signaling pathway. Materials and Methods: After treatment of human colorectal carcinoma cells HCT116 with scutellarin or GANT61, an inhibitor of hedgehog signaling pathway activity as a positive control, at indicated concentrations, the effects of scutellarin or GANT61 on the proliferation, migration and anchorage-independent growth of HCT116 cells were assessed by MTT assay, wound healing assay and soft agar colony formation assay, followed by appraisal of the expressions of mRNA and protein of c-Myc, sonic hedgehog (SHh), Patched 1 (Ptch1) and Gli1 in HCT116 cells with quantitative RT-PCR and western blotting, respectively. Results: Scutellarin inhibited the proliferation, migration and anchorage-independent growth of HCT116 cells and mitigated the expressions of mRNA and protein of c-Myc, SHh, Ptch1 and Gli1 in HCT116 cells in a dose-dependent pattern. Furthermore, GANT61 exhibited strong suppression in above assays as well and the potency of scutellarin at 20 mu g mL(-1) was generally equal to that of GANT61 at 20 mu M. Conclusion: These findings highlighted scutellarin as a promising therapeutic agent for human colorectal cancer, with potential down regulation of hedgehog signaling pathway activity.