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Comparison of microtubules stabilized with the anticancer drugs cevipabulin and paclitaxel

Polymer Journal volume 52, pages 969–976 (2020)Cite this article

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Abstract

Microtubules, one of the major components of the cytoskeleton, play important roles as pathways for neuronal transport of cellular traffic. The loss of structural stability of microtubules causes detrimental effects on neurons and may contribute to several neurodegenerative diseases, such as Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, etc. The triazolopyrimidine class compound cevipabulin is a synthetic microtubule-stabilizing agent that has recently emerged as a drug for the treatment of Alzheimer’s disease. However, the mechanism of microtubule stabilization by cevipabulin has not yet been revealed. Here, we explored the effect of cevipabulin on stabilizing microtubules polymerized from purified tubulins in vitro. We observed the effects of the concentration of microtubule-stabilizing drugs, incubation time, and modification of the cevipabulin structure on the stabilization of microtubules in comparison to those of the most commonly used anticancer drug, paclitaxel. This study will provide insight into the action of cevipabulin in the treatment of neurodegenerative diseases.

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Acknowledgements

This work was financially supported by the Robot Technology Research and Development Project from New Energy and Industrial Technology Development Organization (NEDO), Japan, Grant-in-Aid for Scientific Research on Innovative Areas “Molecular Engine” (JP18H05423 and JP18H03673) and Grant-in-Aid for Young Scientists (A) to AK from the Japan Society for the Promotion of Science (JSPS).

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Authors and Affiliations

  1. Faculty of Science, Hokkaido University, Sapporo, Hokkaido, 060-0810, Japan

    Syeda Rubaiya Nasrin, Arif Md. Rashedul Kabir, Kazuki Sada & Akira Kakugo

  2. Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, 305-8566, Japan

    Tsukasa Ishihara

  3. Department of Computational Intelligence and Systems Science, Tokyo Institute of Technology, Yokohama, 226-8502, Japan

    Akihiko Konagaya

  4. Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo, Hokkaido, 060-0810, Japan

    Kazuki Sada & Akira Kakugo

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  1. Syeda Rubaiya Nasrin
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Correspondence to Akira Kakugo.

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Nasrin, S.R., Ishihara, T., Kabir, A.M.R. et al. Comparison of microtubules stabilized with the anticancer drugs cevipabulin and paclitaxel. Polym J 52, 969–976 (2020). https://doi.org/10.1038/s41428-020-0334-9

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  • DOI: https://doi.org/10.1038/s41428-020-0334-9

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