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Tubulin polymerization-stimulating activity of Ganoderma triterpenoids

Abstract

Tubulin polymerization is an important target for anticancer therapies. Even though the potential of Ganoderma triterpenoids against various cancer targets had been well documented, studies on their tubulin polymerization-stimulating activity are scarce. This study was conducted to evaluate the effect of Ganoderma triterpenoids on tubulin polymerization. A total of twenty-four compounds were investigated using an in vitro tubulin polymerization assay. Results showed that most of the studied triterpenoids exhibited microtuble-stabilizing activity to different degrees. Among the investigated compounds, ganoderic acid T-Q, ganoderiol F, ganoderic acid S, ganodermanontriol and ganoderic acid TR were found to have the highest activities. A structure–activity relationship (SAR) analysis was performed. Extensive investigation of the SAR suggests the favorable structural features for the tubulin polymerization-stimulating activity of lanostane triterpenes. These findings would be helpful for further studies on the potential mechanisms of the anticancer activity of Ganoderma triterpenoids and give some indications on the design of tubulin-targeting anticancer agents.

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Acknowledgements

This paper is in memory of Mr. Ken Sawai, who always encouraged us to work with Ganoderma lingzhi. We also would like to express our gratitude to Mr. Takashi Sawai for providing some of the compounds used in this study. This work was supported by KAKENHI Grant Number 26660147.

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Correspondence to Kuniyoshi Shimizu.

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The authors have declared that there is no conflict of interest.

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T. Kohno, T. Hai-Bang and Q. Zhu contributed equally to this work.

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Kohno, T., Hai-Bang, T., Zhu, Q. et al. Tubulin polymerization-stimulating activity of Ganoderma triterpenoids. J Nat Med 71, 457–462 (2017). https://doi.org/10.1007/s11418-017-1072-y

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Keywords

  • Ganoderma
  • Triterpenes
  • Tubulin polymerization
  • Microtubule
  • Paclitaxel