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Discovery of oxyepiberberine as a novel tubulin polymerization inhibitor and an anti-colon cancer agent against LS-1034 cells

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Summary

Coptis chinensis Franch. has been extensively used in traditional Chinese medicine. The chemical structure of oxyepiberberine, as an alkaloid isolated from Coptis chinensis Franch., has been previously studied. However, anti-cancer effects and underlying mechanisms of oxyepiberberine need to be explored. This study aimed to investigate the anti-cancer effects and underlying mechanisms of oxyepiberberine on LS-1034 human colon cancer cells. The anti-proliferative effects of six derivatives of oxyepiberberine on colon cancer cells were assessed. Among six derivatives, oxyepiberberine showed the greatest anti-proliferative effect on LS-1034 cells with an IC50 value of 1.36 μM. Oxyepiberberine also induced apoptosis and inhibited migration of LS-1034 cells in a concentration-dependent manner. Importantly, oxyepiberberine was identified as a potent tubulin polymerization inhibitor. The tubulin polymerization inhibitory effects of oxyepiberberine in a concentration-dependent manner with an IC50 value of 1.26 μM were observed. A xenograft mouse model of colon cancer showed that oxyepiberberine could suppress tumor growth without an obvious toxicity. Conclusion Oxyepiberberine was found as a novel tubulin polymerization inhibitor, and it could be a promising agent to treat colon cancer.

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Acknowledgments

This work was supported by First Affiliated Hospital of Zhengzhou University.

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Authors and Affiliations

  1. Department of Digestive Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Hanbing Ning, Wenquan Lu, Qiaoyu Jia, Jingyun Wang, Tingting Yao, Shuai Lv, Yingxia Li & Hongtao Wen

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  1. Hanbing Ning
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  2. Wenquan Lu
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  3. Qiaoyu Jia
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  4. Jingyun Wang
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  5. Tingting Yao
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  6. Shuai Lv
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  7. Yingxia Li
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  8. Hongtao Wen
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Contributions

Hanbing Ning designed the project and wrote the paper. Hanbing Ning, Wenquan Lu, Qiaoyu Jia, Jingyun Wang, Tingting Yao, Shuai Lv performed the experiments. Yingxia Li and Hongtao Wen analyzed the data.

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Correspondence to Hanbing Ning.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The manuscript does not contain clinical studies or patient data.

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Ning, H., Lu, W., Jia, Q. et al. Discovery of oxyepiberberine as a novel tubulin polymerization inhibitor and an anti-colon cancer agent against LS-1034 cells. Invest New Drugs 39, 386–393 (2021). https://doi.org/10.1007/s10637-020-01006-0

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  • DOI: https://doi.org/10.1007/s10637-020-01006-0

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