Design, synthesis, and biological activity of a family of novel ceramide analogues in chemoresistant breast cancer cells

J Med Chem. 2009 Sep 24;52(18):5748-52. doi: 10.1021/jm9009668.

Abstract

Resistance to chemotherapy and endocrine therapy is a major cause of breast cancer treatment failure. We have synthesized six novel analogues using C8-ceramide as the lead analogue and studied their effect on hormone therapy resistant (MDA-MB-231) and chemoresistant (MCF-7TN-R) breast cancer cells. Pharmacologic intervention using these ceramide analogues inhibited clonogenic survival and induced apoptosis, with one analogue being more effective than C8-ceramide. Our results show ceramide-based therapy has therapeutic potential in treating drug resistant breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / physiopathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Ceramides / chemical synthesis
  • Ceramides / chemistry*
  • Ceramides / pharmacology*
  • Drug Design*
  • Drug Resistance, Neoplasm*
  • Hormones / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Lysophospholipids / metabolism
  • Sphingosine / analogs & derivatives
  • Sphingosine / metabolism

Substances

  • Antineoplastic Agents
  • Ceramides
  • Hormones
  • Lysophospholipids
  • sphingosine 1-phosphate
  • Sphingosine