Evaluation of the Anti-Proliferative Activity of Rare Aldohexoses against MOLT-4F and DU-145 Human Cancer Cell Line and Structure-Activity Relationship of D-Idose

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  • Ishiyama Hironobu
    Department of Applied Bioresource Science, The United Graduate School of Agricultural Sciences, Ehime University
  • Yanagita Ryo C.
    Department of Applied Biological Science, Faculty of Agriculture, Kagawa University
  • Takemoto Kazune
    Division of Applied Bioresource Science, Graduate School of Agriculture, Kagawa University
  • Kitaguchi Natsumi
    Division of Applied Bioresource Science, Graduate School of Agriculture, Kagawa University
  • Uezato Yuuki
    Division of Applied Bioresource Science, Graduate School of Agriculture, Kagawa University
  • Sugiyama Yasunori
    Department of Applied Biological Science, Faculty of Agriculture, Kagawa University
  • Sato Masashi
    Department of Applied Biological Science, Faculty of Agriculture, Kagawa University
  • Kawanami Yasuhiro
    Department of Applied Biological Science, Faculty of Agriculture, Kagawa University

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Abstract

<p>D-Allose (D-All), a C-3 epimer of D-glucose (D-Glc), is a naturally rare monosaccharide, which shows anti-proliferative activity against several human cancer cell lines. Unlike conventional anticancer drugs, D-All targets glucose metabolism and is non-toxic to normal cells. Therefore, it has attracted attention as a unique “seed” compound for anticancer agents. However, the anti-proliferative activities of the other rare aldohexoses have not been examined yet. In this study, we evaluated the anti-proliferative activity of rare aldohexoses against human leukemia MOLT-4F and human prostate cancer DU-145 cell lines. We found that D-All and D-idose (D-Ido) at 5 mM inhibited cell proliferation of MOLT-4F cells by 46 % and 60 %, respectively. On the other hand, the rare aldohexoses at 5 mM did not show specific anti-proliferative activity against DU-145 cells. To explore the structure–activity relationship of D-Ido, we evaluated the anti-proliferative activity of D-sorbose (D-Sor), 6-deoxy-D-Ido, and L-xylose (L-Xyl) against MOLT-4F cells and found that D-Sor, 6-deoxy-D-Ido, and L-Xyl showed no inhibitory activity at 5 mM, suggesting that the aldose structure and the C-6 hydroxy group of D-Ido are important for its activity. Cellular glucose uptake assay and western blotting analysis of thioredoxin-interacting protein (TXNIP) expression suggested that the anti-proliferative activity of D-Ido is induced by inhibition of glucose uptake via TXNIP-independent pathway.</p>

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