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Citrus unshiu leaf extract containing phytol as a major compound induces autophagic cell death in human gastric adenocarcinoma AGS cells

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An Erratum to this article was published on 28 June 2016

Abstract

The pharmaceutical potential of the methanolic extract of Citrus unshiu leaves (MECL) was assessed through analysis of its inhibitory effect on cancer cells. The antiproliferative activities of the leaves were evaluated using several cancer cell lines and considerable cytotoxicity was observed in human gastric adenocarcinoma AGS cells. Inhibition of AGS cell viability was both time- and dose-dependent, and MECL induced non-apoptotic cell death. AGS cells treated with MECL increased the formation of acidic vesicular organelles and GFP-LC3 puncta. Pretreatment with an autophagy inhibitor, 3-methyladenine, inhibited MECL-induced cell death. These results indicated that the mechanism underlying the anticancer effects of MECL in AGS cells could be via the induction of autophagic cell death. The major compounds of MECL were identified as phytol, 4-ethenyl-2-methoxyphenol, hexadecanoic acid, 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, and vitamin E using gas chromatography–mass spectrometry. These results indicate that C. unshiu leaves can be exploited for numerous pharmaceutical applications as a source of anticancer ingredients.

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Acknowledgments

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2014047495) and by the Ministry of Education (2013R1A1A2A10012017). This work was done while the author has research year Jeju National University in 2013.

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Correspondence to Somi Kim Cho.

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Song, Y.W., Shrestha, S., Gyawali, R. et al. Citrus unshiu leaf extract containing phytol as a major compound induces autophagic cell death in human gastric adenocarcinoma AGS cells. J Korean Soc Appl Biol Chem 58, 257–265 (2015). https://doi.org/10.1007/s13765-015-0026-x

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