Cholesterol level of lipid raft microdomains regulates apoptotic cell death in prostate cancer cells through EGFR-mediated Akt and ERK signal transduction.
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.
Oh
Hea Young
HY
Department of Urology, Urological Science Institute, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea.
Lee
Eun Jin
EJ
Yoon
Sun
S
Chung
Byung Ha
BH
Cho
Kang Su
KS
Hong
Sung Joon
SJ
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002784:Cholesterol / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008297:Male; D021962:Membrane Microdomains / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000503:physiopathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D051020:bcl-X Protein / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000494:pharmacology
C494811:BCL2L1 protein, human; D051020:bcl-X Protein; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002784:Cholesterol; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3