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Costunolide and dehydrocostuslactone from Saussurea lappa root inhibit autophagy in hepatocellular carcinoma cells

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Abstract

Autophagy is a catabolic process for degradation of intracellular components and plays an important role in the development and growth of cancer. Our preliminary screening confirmed that an extract from the root of Saussurea lappa remarkably suppressed the proliferation of HepG2 hepatocellular carcinoma cells and inhibited autophagy. In this study, we explored the effects of costunolide (CL) and dehydrocostuslactone (DCL), which are bioactive sesquiterpene lactones in this extract, on autophagy modulation in HepG2 cells. An analysis of autophagy-related proteins demonstrated that CL and DCL blocks the autophagy process that leads to the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 (p62). LC3 turnover assays indicated that CL and DCL trigger autophagy inhibition by blocking the autophagic flux, thereby resulting in the accumulation of LC3-II and p62. These results are encouraging and warrant further study of CL and DCL for potential use as autophagy inhibiting agents for liver cancer therapy.

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Acknowledgements

This study was partly supported by the Sasakawa Scientific Research Grant from The Japan Science Society (Grant Number 2018-4039). This work was also funded by JSPS KAKENHI Grant Number 19K07145 and 25871011.

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Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch-Cho, Sasebo, Nagasaki, 859-3298, Japan

    Shinya Okubo, Hideaki Fujita & Takuhiro Uto

  2. Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch-Cho, Sasebo, Nagasaki, 859-3298, Japan

    Tomoe Ohta, Hideaki Fujita, Yukihiro Shoyama & Takuhiro Uto

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  1. Shinya Okubo
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  2. Tomoe Ohta
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  3. Hideaki Fujita
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  5. Takuhiro Uto
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Correspondence to Takuhiro Uto.

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Okubo, S., Ohta, T., Fujita, H. et al. Costunolide and dehydrocostuslactone from Saussurea lappa root inhibit autophagy in hepatocellular carcinoma cells. J Nat Med 75, 240–245 (2021). https://doi.org/10.1007/s11418-020-01462-1

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  • DOI: https://doi.org/10.1007/s11418-020-01462-1

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