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
Open Access
- 1 January 2020
- journal article
- research article
- Published by The Japanese Society of Applied Glycoscience in Journal of Applied Glycoscience
- Vol. 67 (3), 95-101
- https://doi.org/10.5458/jag.jag.JAG-2020_0006
Abstract
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.This publication has 21 references indexed in Scilit:
- Analysis of UDP-d-Apiose/UDP-d-Xylose Synthase-Catalyzed Conversion of UDP-d-Apiose Phosphonate to UDP-d-Xylose Phosphonate: Implications for a Retroaldol–Aldol MechanismJournal of the American Chemical Society, 2012
- Glucose sensing by ChREBP/MondoA–Mlx transcription factorsSeminars in Cell & Developmental Biology, 2012
- Switching from aerobic glycolysis to oxidative phosphorylation modulates the sensitivity of mantle cell lymphoma cells to TRAILOncogene, 2012
- Anti-oxidative effects of d-allose, a rare sugar, on ischemia-reperfusion damage following focal cerebral ischemia in ratNeuroscience Letters, 2011
- Analysis of the inhibitory mechanism of d-allose on MOLT-4F leukemia cell proliferationJournal of Bioscience and Bioengineering, 2009
- Rare sugar d-allose induces programmed cell death in hormone refractory prostate cancer cellsApoptosis, 2008
- Potential anthelmintic: d-psicose inhibits motility, growth and reproductive maturity of L1 larvae of Caenorhabditis elegansJournal of Natural Medicines, 2008
- Chemical properties and antioxidative activity of glycated α-lactalbumin with a rare sugar, d-allose, by Maillard reactionFood Chemistry, 2006
- Izumoring: A novel and complete strategy for bioproduction of rare sugarsJournal of Bioscience and Bioengineering, 2004
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970