Growth inhibitory effect of D-allose on human ovarian carcinoma cells in vitro.

BACKGROUND D-allose is a rare sugar found in nature and, because of its very limited amount and of the high cost associated with its synthesis, its physiological functions remain virtually unknown. The aim of the current study was to investigate the effect of D-allose on the proliferation of human ovarian carcinoma cells in vitro. MATERIALS AND METHODS Human ovarian carcinoma cells (OVCAR-3 cell line) were exposed to rare sugars including D-allose, D-altrose, D-psicose and D-talitol. Cell growth was evaluated by MTT assay. Cell cycle analysis was carried out by flow cytometric assay. The expression of cell cycle regulatory proteins was determined by Western blot analysis. TUNEL assay was employed for the detection of apoptotic cells. RESULTS D-allose had a significant inhibitory effect on ovarian cancer cell proliferation in a dose-dependent manner, and caused a moderate G2/M arrest in the cell cycle, up-regulation of Cdk inhibitors p21 and p27 levels, and the induction of apoptosis in OVCAR-3 cells. CONCLUSION Our results show, for the first time, that D-allose inhibits the growth of ovarian carcinoma cells in vitro. Although the exact mechanisms remain unclear, these findings suggest that D-allose possesses a novel inhibitory property on ovarian carcinoma cell proliferation, and may represent a new class of compounds with possible therapeutic potential.

[1]  K. Izumori Bioproduction strategies for rare hexose sugars , 2002, Naturwissenschaften.

[2]  C. Sherr The Pezcoller lecture: cancer cell cycles revisited. , 2000, Cancer research.

[3]  E. Newsholme,et al.  Novel monosaccharides as potent inhibitors of cell proliferation , 1997, Cell biochemistry and function.

[4]  A. Hart,et al.  The Baxα:Bcl‐2 ratio modulates the response to dexamethasone in leukaemic cells and is highly variable in childhood acute leukaemia , 1997, International journal of cancer.

[5]  Z. Oltvai,et al.  Multiple Bcl-2 family members demonstrate selective dimerizations with Bax. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[6]  R. Germinario,et al.  Evidence that modulation of glucose transporter intrinsic activity is the mechanism involved in the allose‐mediated depression of hexose transport in mammalian cells , 1994, Journal of cellular physiology.

[7]  David Beach,et al.  p21 is a universal inhibitor of cyclin kinases , 1993, Nature.

[8]  S. Elledge,et al.  The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases , 1993, Cell.

[9]  C. Franceschi,et al.  Inhibition of Cell Proliferation by D-Ribose and Deoxy-D-ribose , 1985, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[10]  J. Decker,et al.  Evidence that specific oligosaccharides block early events necessary for the expression of antigen-specific proliferation by human lymphocytes. , 1980, Journal of immunology.

[11]  O. Stutman,et al.  Natural cytotoxic cells against solid tumors in mice: blocking of cytotoxicity by D-mannose. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[12]  L. Doner Isomerization of d-fructose by base: Liquid-chromatographic evaluation and the isolation of d-psicose , 1979 .

[13]  T. Yoshida,et al.  Suppression of cell-mediated immune reactions by monosaccharides. , 1979, Journal of immunology.

[14]  R. Rocklin Role of monosaccharides in the interaction of two lymphocyte mediators with their target cells. , 1976, Journal of immunology.

[15]  E. Mcdonald A new synthesis of d-psicose (d-ribo-hexulose) , 1967 .

[16]  Yasuo Watanabe,et al.  A novel inhibitory effect of D-allose on production of reactive oxygen species from neutrophils. , 2003, Journal of bioscience and bioengineering.

[17]  T. Katayama,et al.  D-Allose Production from D-Psicose Using Immobilized L-Rhamnose Isomerase , 1998 .

[18]  K. Izumori,et al.  Preparation of d-psicose from d-fructose by immobilized d-tagatose 3-epimerase , 1995 .