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Tumor specific cytotoxicity of glucosylceramide

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Abstract

To develop a new taxon of anti-cancer agent with lower side effect, this study described a tumor selective cytotoxicity of glucosylceramide extracted from malt feed of beer brewing waste. Interpretation of 13C- and 1H-NMR spectra identified the chemical structure of major component of glucosylceramide as 1-O-β-d-glucopyranosyl-2(2′-hydroxyeicosanoylamino)-4,11-octadecadiene-1,3-diol. Selective cytotoxicity was studied with three pairs of normal and cancer cells: liver, skin and lung. The glucosylceramide selectively lowered the relative viability of cancer cells. Of the pairs, the selectivity was most pronounced with the liver cells, and, for this reason, further experiment was conducted with this pair of normal (CS-HC) and cancer cells (HepG2) to get more insight into the selective toxicity. The glucosylceramide significantly increased the cell population at G2/M phase in HepG2 cells, and also increased the numbers of apoptotic (sub-G0/G1) cells, but to much lesser extent compared with the increase in G2/M phase. Treatment of HepG2 cells with this agent selectively disrupted the mitochondrial membrane integrity without activation of caspase pathway to induce apoptosis. These findings suggested that the glucosylceramide specifically suppressed the growth of cancer cells by inhibiting cell renewal capacity rather than induction of apoptosis. The underlying mechanism for the selectivity remains to be answered in the forthcoming study.

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Acknowledgment

The authors thank Ms. Shiho Tomori for her excellent technical assistance, and our thanks also go to Orion Beer Co. and DNA bank Co. for the preparation of crude ceramide from malt feed.

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Authors and Affiliations

  1. Center of Molecular Biosciences, University of the Ryukyus, Nishihara, Okinawa, 903-0213, Japan

    Hirosuke Oku, Sawitree Wongtangtintharn & Hironori Iwasaki

  2. United Graduate School of Agricultural Sciences, Kagoshima University, 1-21-24, Korimoto, Kagoshima, 890-0065, Japan

    Masashi Inafuku

  3. Graduate School of Agriculture, University of the Ryukyus, Nishihara, Okinawa, 903-0213, Japan

    Masayuki Shimatani

  4. Department of Clinical Laboratory Medicine, University of the Ryukyus Hospital, School of Medicine, Uehara 207, Nishihara, Okinawa, 903-0125, Japan

    Takayoshi Toda

Authors
  1. Hirosuke Oku
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  2. Sawitree Wongtangtintharn
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  3. Hironori Iwasaki
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  4. Masashi Inafuku
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  5. Masayuki Shimatani
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  6. Takayoshi Toda
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Correspondence to Hirosuke Oku.

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Oku, H., Wongtangtintharn, S., Iwasaki, H. et al. Tumor specific cytotoxicity of glucosylceramide. Cancer Chemother Pharmacol 60, 767–775 (2007). https://doi.org/10.1007/s00280-007-0422-y

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  • DOI: https://doi.org/10.1007/s00280-007-0422-y

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