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

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posted on 2019-03-31, 13:44 authored by Hae Min So, Seul Lee, Kwan-Hyuck Baek, Hyun-Soo Roh, Sil Kim, Mun Seok Jo, Su Cheol Baek, Soonja Seok, Rhim Ryoo, Ki Hyun Kim

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.

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.

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