2-Deoxy-L-ribose inhibits the invasion of thymidine phosphorylase-overexpressing tumors by suppressing matrix metalloproteinase-9

Int J Cancer. 2006 Oct 1;119(7):1710-6. doi: 10.1002/ijc.22014.

Abstract

Thymidine phosphorylase (TP), an enzyme involved in pyrimidine metabolism, is identical with an angiogenic factor, platelet-derived endothelial cell growth factor. 2-Deoxy-D-ribose (D-dRib), the degradation product of thymidine generated by TP activity, has been suggested to be a downstream mediator of TP function. 2-Deoxy-L-ribose (L-dRib), a stereoisomer of D-dRib, inhibited the promotion of angiogenesis, tumor growth and metastasis by TP. In our study, we have shown that nude mice inoculated with TP-overexpressing KB/TP cells had shorter survival times than those injected with control KB/CV cells. KB/TP tumors were also more highly invasive than KB/CV tumors in mice. The expression levels of matrix metalloproteinase (MMP)-9 in KB/TP tumors were significantly higher than those in KB/CV tumors. L-dRib and a TP inhibitior, TPI, extended the survival period of KB/TP tumor-bearing mice. L-dRib also reduced MMP-9 mRNA levels in KB/TP tumors. Furthermore, L-dRib suppressed the mRNA level of MMP-9 in cultured KB/TP cells, and the invasive activity of the cells. L-dRib may be useful for the suppression of invasion of TP-expressing tumor cells.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Culture Media
  • Deoxyribose / pharmacology*
  • Gene Expression* / genetics
  • Humans
  • Intestinal Neoplasms / genetics
  • Intestinal Neoplasms / metabolism
  • Intestinal Neoplasms / prevention & control
  • Intestinal Neoplasms / secondary
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / prevention & control
  • Liver Neoplasms / secondary
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness / prevention & control
  • Survival Rate
  • Thymidine Phosphorylase / genetics
  • Thymidine Phosphorylase / metabolism*

Substances

  • Culture Media
  • Deoxyribose
  • Thymidine Phosphorylase
  • Matrix Metalloproteinase 9