2'-Deoxycytidine decreases the anti-tumor effects of 5-fluorouracil on mouse myeloma cells.
2'-Deoxycytidine (dCyd), a pyrimidine nucleoside found at high concentrations in the plasma of cancer patients with a poor prognosis after chemotherapy, is considered to be a biomarker for breast cancer. 5-Fluorouracil (5FU) is a nucleoside analog and is used as an anti-tumor agent in patients whose plasma dCyd concentrations are increased. Because both dCyd and 5FU are pyrimidine analogues, it is possible that they have pharmacokinetic/ pharmacodynamic interaction, by which the anti-cancer efficacy of 5FU would be reduced. Here, we examined the effects of dCyd on the cytotoxicity of 5FU on mouse myeloma SP2/0-Ag14 (SP2/0) cells lacking hypoxanthine-guanine-phosphoribosyl transferase (HGPRT) and RH4 hybridomas with HGPRT under asynchronized conditions. The reduced cell viability by 5FU was restored by co-, but not pre-, treatment of dCyd in both SP2/0 and RH4 cells, but this effect in the former tended to be greater than that in the latter, suggesting a possible involvement of HGPRT in the interaction, although this might not be a major mechanism. Moreover, dCyd administration to SP2/0 myeloma-bearing mice tended to shorten their 5FU-induced prolonged survival in vivo. Collectively, these results indicate that dCyd decreases the anti-tumor efficacy of 5FU and that a metabolic pathway via HGPRT is involved partially in this interaction. The evaluation of dCyd as a biomarker is believed to provide valuable information for effective and safe chemotherapy with 5FU.
Iwazaki
Ayano
A
Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan. ayano@pharm.setsunan.ac.jp
Yoshioka
Masanori
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D003841:Deoxycytidine / Q000378:metabolism* / Q000494:pharmacology; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use*; D006825:Hybridomas; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism*; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D015415:Biomarkers; D003841:Deoxycytidine; D007041:Hypoxanthine Phosphoribosyltransferase; D005472:Fluorouracil