Sphingomyelin potentiates chemotherapy of human cancer xenografts

Biochem Biophys Res Commun. 2000 Feb 16;268(2):603-6. doi: 10.1006/bbrc.2000.2178.

Abstract

We propose that one manifestation of altered sphingolipid metabolism within tumor cells may be a reduced sensitivity to anti-cancer therapies because of an inability to produce a sufficient apoptotic signal via sphingomyelin hydrolysis to ceramide. If so, then sphingomyelin administration could reverse this effect and increase a tumor's sensitivity to chemotherapy. In vivo, intravenous sphingomyelin (10 mg/day, 7 days) potentiated 5-fluorouracil chemotherapy (0.45 mg/day, 5 days) when co-administered to HT29 human colonic xenograft-bearing nude mice. In vitro, sphingomyelin (SM) at its maximum tolerated concentration increased 5-fluorouracil and doxorubicin sensitivity of HCT15 and MOSER (1 mg/ml SM) and LS174T and SW480 human colonic tumor cells (0.1 mg/ml) approximately 100-300%. At 1 mg/ml SM, however, no effect was seen using HT29, LoVo and WiDr cells. There was no sensitization of normal human umbilical cord endothelial cells. Thus, sphingomyelin co-administration may be one method to improve the selective efficacy of chemotherapy in some tumors, possibly through enhancement of the apoptotic response.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Colonic Neoplasms / drug therapy*
  • Disease Models, Animal
  • Drug Synergism
  • Fluorouracil / therapeutic use*
  • Humans
  • Injections, Intravenous
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Experimental / drug therapy*
  • Sphingomyelins / therapeutic use*
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • Antimetabolites, Antineoplastic
  • Sphingomyelins
  • Fluorouracil