Bioactivity-based analysis and chemical characterization of cytotoxic compounds from a poisonous mushroom, Amanita spissacea, in human lung cancer cells in vitro

Abstract

As part of our systematic study on Korean toxic mushrooms, bioactivity-guided fractionation of the MeOH extract of Amanita spissacea (Amanitaceae) fruiting bodies and chemical investigation of its cytotoxic fractions led to the isolation of (9E)-8-oxo-9-octadecenoic acid (1), (10E)-9-oxo-10-octadecenoic acid (2), (9E)-8-oxo-9-octadecenoate methyl ester (3), (9Z)-9-octadecenoate-(2'S)-2',3'-dihydroxypropyl ester (4), (9Z)-9-octadecenoic acid (5), and palmitic acid (6). The structures of the isolates were elucidated by NMR spectroscopic analysis and LC/MS analysis. Among the isolated compounds, compounds 1 and 2 exhibited the most potent cytotoxic activity in all human lung cancer cell lines examined, with IC₅₀ values ranging from 255.7 to 321.0 μM and 250.2 to 322.5 μM, respectively. The cytotoxicity of these compounds was also found to be mediated by apoptosis associated with caspase-3 activation. These findings provide experimental evidence suggesting the potential of A. spissacea as a promising natural source for the discovery of novel anticancer drug candidates.

Graphical Abstract

Keywords:

• Amanita spissacea
• poisonous mushroom
• fatty acids
• cytotoxicity
• lung cancer
• apoptosis

Acknowledgements

We would like to thank Dr. Young Hye Kim (Korea Basic Science Institute) for ESI-MS analysis.

Disclosure statement

The authors have declared no conflict of interest.

Additional information

Funding

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2018R1A2B2006879). This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2012R1A5A2A28671860). Seul Lee was supported by the NRF-2015-Global PhD Fellowship Program of the National Research Foundation of Korea (NRF), which is funded by the Korean Government (NRF-2015H1A2A1034135). This study was supported by biological toxicity research (KNA 1-3-2, 19-5) of the National Institute of Forest Science affiliated with the Korea Forest Service.