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

International Journal of Cancer. Journal International Du Cancer
Yuichi NakajimaShin-ichi Akiyama

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.

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Citations

Apr 1, 2010·World Journal of Gastroenterology : WJG·Jongkonnee ThanasaiMasanao Miwa
May 13, 2009·Medicinal Research Reviews·Annelies BronckaersSandra Liekens
Jun 19, 2007·Biochemical Pharmacology·Sandra LiekensJan Balzarini
Aug 25, 2015·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Yasir Y ElaminKathy Gately
May 23, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Qiang ZhangCheng Yang
Nov 27, 2018·The Journal of Organic Chemistry·Wei-Syun SongChe-Chien Chang

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