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Pulveraven A from the fruiting bodies of Pulveroboletus ravenelii induces apoptosis in breast cancer cell via extrinsic apoptotic signaling pathway

The Journal of Antibiotics volume 74, pages 752–757 (2021)Cite this article

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Abstract

Pulveroboletus ravenelii (Beck. et Curt.) Murr. (Boletaceae), commonly known as Ravenel’s bolete, is an edible and medicinal mushroom, and is also used for preparing mushroom-based dyes. As part of a continuing project to discover the bioactive natural products from wild mushrooms, we analyzed the methanol (MeOH) extract of P. ravenelii to identify metabolites with the anticancer activity. Chemical analysis of the MeOH extract combined with liquid chromatography–mass spectrometry (LC–MS) analysis led to the isolation of a phenolic compound, pulveraven A (PA), whose chemical structure was determined using a combination of 1D and 2D NMR and LC–MS analysis. In the present study, we investigated the cytotoxicity and anticancer mechanisms of pulveraven A using human breast cancer (MCF-7) cells, and demonstrated that it reduced cell viability of MCF-7 cells below 50% (71.74 ± 3.61 μM). Annexin V Alexa Fluor 488 binding assay and western blot results revealed that pulveraven A induced apoptotic cell death via the extrinsic apoptosis pathway, as indicated by the activation of initiator caspase-8 and executioner caspase-7. Furthermore, it was accompanied by an increase in the Bax/Bcl-2 ratio. These results suggest that pulveraven A induces apoptosis in breast cancer cells via the extrinsic apoptotic signaling pathway.

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Acknowledgements

This work was supported by a grant from the National Research Foundation of Korea (NRF), funded by the Korean government (MSIT) (2019R1A5A2027340), and the Korea Institute of Science and Technology intramural research grant (2E30641). This work was also supported by the Nano Convergence Industrial Strategic Technology Development Program (20000105, Development of Cosmeceutical Material Platform using Organo-Nano Complexes based on Natural Active Compounds) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea).

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Author notes

  1. These authors contributed equally: Dahae Lee, Jae Sik Yu

Authors and Affiliations

  1. College of Korean Medicine, Gachon University, Seongnam, Republic of Korea

    Dahae Lee & Ki Sung Kang

  2. Natural Product Research Laboratory, School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea

    Jae Sik Yu & Ki Hyun Kim

  3. Special Forest Products Division, Forest Bioresources Department, National Institute of Forest Science, Suwon, Republic of Korea

    Rhim Ryoo

  4. KIST Gangneung Institute of Natural Products, Natural Product Informatics Research Center, Gangneung, Republic of Korea

    Jin-Chul Kim

  5. Department of Medicine, Dankook University, Cheonan, Chungnam, Republic of Korea

    Tae Su Jang

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  1. Dahae Lee
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Correspondence to Ki Sung Kang or Ki Hyun Kim.

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Lee, D., Yu, J.S., Ryoo, R. et al. Pulveraven A from the fruiting bodies of Pulveroboletus ravenelii induces apoptosis in breast cancer cell via extrinsic apoptotic signaling pathway. J Antibiot 74, 752–757 (2021). https://doi.org/10.1038/s41429-021-00435-0

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