Distinctive molecular signaling in triple-negative breast cancer cell death triggered by hexadecylphosphocholine (miltefosine)

FEBS Lett. 2008 Dec 24;582(30):4176-84. doi: 10.1016/j.febslet.2008.11.019. Epub 2008 Nov 28.

Abstract

This study describes the molecular signaling involved in the different cell death modes of triple-negative breast cancer cells induced by hexadecylphosphocholine (HePC/miltefosine), a clinically relevant anticancer alkylphosphocholine. We found that the HePC treatment triggers cell-type-dependent apoptotic and non-apoptotic cell death processes. Moreover, the expression level of the apoptosis activator Fas, and Fas/Fas ligand signaling capacity are not attributing factors for the preference toward apoptosis. Using Fas siRNA and overexpression approaches we establish that Fas is not a pro-apoptotic factor but a contributor to cell protection in HePC-apoptosis-sensitive cells. The insight in the multi-modal anticancer capability of HePC in triple-negative breast cancer cells may facilitate the targeted design of therapeutic strategies against triple-negative breast cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis* / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / metabolism
  • Humans
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Small Interfering / genetics
  • Signal Transduction / drug effects
  • fas Receptor / genetics
  • fas Receptor / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antineoplastic Agents
  • Fas Ligand Protein
  • RNA, Small Interfering
  • fas Receptor
  • Phosphorylcholine
  • miltefosine
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases