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

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Abstract

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 β-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 β-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 β-catenin pathway was attributed to the promotion of β-catenin degradation by inhibition of GSK3β phosphorylation. When the phosphorylation of GSK3β was induced by LiCl, the inhibitory effect of CleA on the β-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 β-catenin pathway.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31671206, 31500965, 31471141, and 81702874). We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

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Authors and Affiliations

  1. Institute of Special Environmental Medicine, Nantong University, 9 Seyuan Road, Nantong, 226019, China

    Siyuan Liu, Lu Wang, Wangwang Ding, Dan Wang, Xueting Wang, Qianqian Luo, Yapeng Lu & Li Zhu

  2. Center of Analysis and Testing, Nantong University, Nantong, 226019, China

    Siyuan Liu

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  1. Siyuan Liu
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Liu, S., Wang, L., Ding, W. et al. Cleistanthin A inhibits the invasion of MDA-MB-231 human breast cancer cells: involvement of the β-catenin pathway. Pharmacol. Rep 72, 188–198 (2020). https://doi.org/10.1007/s43440-019-00012-1

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