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Anti-metastatic effects of ergosterol peroxide from the entomopathogenic fungus Ophiocordyceps gracilioides on 4T1 breast cancer cells

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Abstract

Ophiocordyceps gracilioides is an entomoparasitic ascomycetes whose bioactivity has not been examined in detail. In this study, we identified the bioactive compounds ergosterol peroxide (EPO) and ergosterol (ERG) from the MeOH extract of O. gracilioides mycelia related to its anti-cancer effects by targeting the Nuclear Factor kappa B (NF-ĸB)/Signal Transducer and Activator of Transcription 3 (STAT3) inflammatory pathways. Using gene-reporter assays, we demonstrated that EPO markedly inhibits both NF-ĸB and STAT3 activity in 4T1 cells, whereas ERG had limited effect. Consistent with their effects on NF-ĸB and STAT3 activity, EPO, but not ERG, exerted anti-proliferative effects on 4T1 cells. Furthermore, EPO significant inhibited both the migration and invasion of 4T1 cells in vitro, and pre-treatment of 4T1 cells with EPO significantly inhibited the formation of experimental lung metastases in vivo. Collectively, we demonstrated that ERG and EPO can be isolated from O. gracilioides mycelia, and further identified EPO as an active constituent of its anti-metastatic effects through the inhibition of NF-ĸB and STAT3 inflammatory pathways in 4T1 breast cancer cells.

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Acknowledgements

This study was supported by a grant from the Frontier Research Program of Toyama Prefecture. M-K.S. was supported by a scholarship from the Rotary Yoneyama Memorial Foundation.

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  1. Hiroyuki Morita and Yoshihiro Hayakawa contributed equally to this work.

Authors and Affiliations

  1. Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Min-Kyoung Shin, Dae-Won Ki, Nwet Nwet Win, Hiroyuki Morita & Yoshihiro Hayakawa

  2. Forestry Research Institute, Toyama Prefectural Agricultural, Forestry and Fisheries Research Center, Toyama, Japan

    Fumito Sasaki

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  1. Min-Kyoung Shin
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Shin, MK., Sasaki, F., Ki, DW. et al. Anti-metastatic effects of ergosterol peroxide from the entomopathogenic fungus Ophiocordyceps gracilioides on 4T1 breast cancer cells. J Nat Med 75, 824–832 (2021). https://doi.org/10.1007/s11418-021-01520-2

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