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Glochidiol, a natural triterpenoid, exerts its anti-cancer effects by targeting the colchicine binding site of tubulin

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Summary

Glochidiol has been shown to have potentially antiproliferative activity in vitro, however its anticancer mechanisms specifically against lung cancer remain unknown. This study aimed to investigate the anti-lung cancer effects of glochidiol in HCC-44 cells in vitro and in vivo. In the present study, glochidiol was found to have potent antiproliferative activity against lung cancer cell lines NCI-H2087, HOP-62, NCI-H520, HCC-44, HARA, EPLC-272H, NCI-H3122, COR-L105 and Calu-6 with IC50 values of 4.12 µM, 2.01 µM, 7.53 µM, 1.62 µM, 4.79 µM, 7.69 µM, 2.36 µM, 6.07 µM and 2.10 µM, respectively. In vivo, glochidiol was found to effectively inhibit lung cancer HCC-44 xenograft tumor growth in nude mice. Docking analysis found that glochidiol forms hydrogen bonds with residues of tubulin. Glochidiol was also found to inhibit tubulin polymerization in vitro with an IC50 value of 2.76 µM. Immunofluorescence staining and EBI competition assay suggest that glochidiol may interact with tubulin by targeting the colchicine binding site. Thus, glochidiol might be a novel colchicine binding site inhibitor with the potential to treat lung cancer.

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Acknowledgements

Thanks for the support from First Affiliated Hospital of Zhengzhou University.

Funding

We thank the financial support from First Affiliated Hospital of Zhengzhou University.

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Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China

    Hongjie Chen, Lijun Miao, Fengxiang Huang, Yali Yu, Qiang Peng, Ying Liu, Xixi Li & Hong Liu

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  1. Hongjie Chen
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  2. Lijun Miao
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  3. Fengxiang Huang
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  4. Yali Yu
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  5. Qiang Peng
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  6. Ying Liu
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  7. Xixi Li
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  8. Hong Liu
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Correspondence to Hong Liu.

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Conflict of interest

All authors have declared that they have no conflicts of interest to disclose. Hongjie Chen declares that he has no conflict of interest. Lijun Miao declares that she has no conflict of interest. Fengxiang Huang declares that she has no conflict of interest. Yali Yu declares that she has no conflict of interest. Qiang Peng declares that he has no conflict of interest. Ying Liu declares that she has no conflict of interest. Xixi Li declares that she has no conflict of interest. Hong Liu declares that she has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Ethics Committee of Zhengzhou University approved this experiment (No. 2019-CHJ07). All procedures performed in studies involving animals were in accordance with the ethical standards of the ethics committee of Zhengzhou University (Zhengzhou, Henan Province, China).

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Chen, H., Miao, L., Huang, F. et al. Glochidiol, a natural triterpenoid, exerts its anti-cancer effects by targeting the colchicine binding site of tubulin. Invest New Drugs 39, 578–586 (2021). https://doi.org/10.1007/s10637-020-01013-1

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