title: Deoxyribose protects against rapamycin-induced cytotoxicity in colorectal cancer cells in vitro.
abstract: Thymidine phosphorylase (TPase) is also known as the platelet-derived endothelial cell growth factor (PD-ECGF) and plays a role in angiogenesis. Deoxyribose (dR; a downstream TPase-product) addition to endothelial cells may stimulate FAK and p70/S6k signaling, which can be inhibited by rapamycin. Rapamycin is a specific mammalian target of the rapamycin (mTOR) inhibitor, a kinase that lies directly upstream of p70/S6k. This suggests a role for TPase in the mTOR/p70/S6k pathway. In order to study this in more detail, we exposed cells with and without TPase expression to dR and rapamycin and determined the effect on cell growth. We observed protection in cytotoxicity in Colo320 cells, but not Colo320 TP1 cells. This was in part mediated by activation of p70/S6k and inhibition of autophagy. Further studies are recommended to elucidate the mechanism behind the protective effect of dR.
authors: Department of Urology, VU University Medical Center, Amsterdam, The Netherlands.
authors: I V
authors: IV
authors: Bijnsdorp
authors: G J
authors: GJ
authors: Peters
mesh_terms: D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000473:pathology*; D019610:Cytoprotection / Q000187:drug effects*; D003855:Deoxyribose / Q000494:pharmacology* / Q000627:therapeutic use; D005455:Fluorescent Antibody Technique; D006801:Humans; D020128:Inhibitory Concentration 50; D042541:Intracellular Space / Q000187:drug effects / Q000201:enzymology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020123:Sirolimus / Q000633:toxicity*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D003855:Deoxyribose; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus