Cholesterol level of lipid raft microdomains regulates apoptotic cell death in prostate cancer cells through EGFR-mediated Akt and ERK signal transduction

Prostate. 2007 Jul 1;67(10):1061-9. doi: 10.1002/pros.20593.


Background: Lipid rafts are cholesterol-enriched microdomains in cell membranes that have been shown to regulate signal transduction. We investigated whether membrane cholesterol could regulate apoptosis and attempted to elucidate the mechanism by which apoptosis is induced in prostate cancer cells.

Methods: LNCaP cells were exposed to 2-hydroxyprophyl-beta-cyclodextrin (HPCD) to deplete membrane cholesterol. Cell viability and apoptosis were evaluated by Celltiter Bluetrade mark Cell Viability assay and ethidium bromide/acridine orange staining. Signal transduction was investigated by immunoblot analysis of cell lysates.

Results: Cell viability was dose dependent inhibited by HPCD and restored by replenishment of cholesterol. HPCD induced apoptotic cell death through down-regulation of Bcl-xL and up-regulation of caspase-3 and PARP cleavages. HPCD inhibited both EGFR/Akt and EGFR/ERK signal transduction.

Conclusions: Lipid raft cholesterol regulates apoptotic cell death in prostate cancer cells through EGFR-mediated Akt and ERK pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cholesterol / physiology*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • ErbB Receptors / genetics
  • ErbB Receptors / physiology*
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Male
  • Membrane Microdomains / physiology*
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / physiopathology
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / physiology*
  • Signal Transduction / physiology
  • Up-Regulation / drug effects
  • bcl-X Protein / metabolism
  • beta-Cyclodextrins / pharmacology


  • BCL2L1 protein, human
  • bcl-X Protein
  • beta-Cyclodextrins
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Cholesterol
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Caspase 3