Cleistanthin A inhibits the invasion of MDA-MB-231 human breast cancer cells: involvement of the β-catenin pathway

Background: Cleistanthin A (CleA), a natural diphyllin glycoside, has been shown to suppress the invasion of cancer cells, but the underlying mechanisms remain unclear. Here, the inhibitory effect of CleA on the invasion of MDA-MB-231 human breast cancer cells was investigated, and the mechanisms involved were clarified. Methods: Cell viability was studied by MTT assay. The migration and invasion of MDA-MB-231 cells were assessed by wound healing assay and transwell assay, respectively. The enzymatic activity of matrix metalloproteinases (MMPs) was detected by gelatin zymography. mRNA and protein levels were detected by qRT-PCR and Western blotting, respectively. Nuclear translocation of beta-catenin was observed by immunofluorescence and detected by Western blotting. Results: CleA effectively inhibited the migration and invasion of MDA-MB-231 cells and suppressed the expression and activation of MMP-2/9. Moreover, the expression and nuclear translocation of beta-catenin were reduced by CleA treatment, as well as transcription of the Cyclin D1 and c-myc genes. In addition, the inhibitory effect of CleA on the beta-catenin pathway was attributed to the promotion of beta-catenin degradation by inhibition of GSK3 beta phosphorylation. When the phosphorylation of GSK3 beta was induced by LiCl, the inhibitory effect of CleA on the beta-catenin pathway and the invasion of MDA-MB-231 cells were almost reversed. Conclusion: CleA suppressed the invasion of MDA-MB-231 cells, likely through the beta-catenin pathway.