Sphingosine-1-phosphate: a potential therapeutic agent against human breast cancer

Invest New Drugs. 2011 Apr;29(2):396-9. doi: 10.1007/s10637-009-9375-9. Epub 2009 Dec 30.

Abstract

Sphingosine-1-phosphate (S1P) is an important regulator of cancer development and progression. Its cellular concentration is controlled predominantly by sphingosine kinase (SK) and sphingosine-1-phosphate lyase (SPL). In the current study we showed that mRNA expressions for both SK and SPL were up-regulated throughout all four disease stages in human breast cancer patients. Exogenous administration of S1P produced a bell-shaped dose response for apoptosis in normal mammary gland MCF12A cells but a sigmoid-shaped apoptotic response in breast cancer MCF7 cells. Co-administration of S1P enhanced the cytotoxicity of anticancer drug docetaxel against MCF7 cells.

MeSH terms

  • Aldehyde-Lyases / genetics
  • Aldehyde-Lyases / metabolism
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Docetaxel
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lysophospholipids / pharmacology
  • Lysophospholipids / therapeutic use*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Sphingosine / therapeutic use
  • Taxoids / pharmacology

Substances

  • Lysophospholipids
  • RNA, Messenger
  • Taxoids
  • Docetaxel
  • sphingosine 1-phosphate
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase
  • Aldehyde-Lyases
  • sphingosine 1-phosphate lyase (aldolase)
  • Sphingosine