5,8,11,14-eicosatetraynoic acid-induced destruction of mitochondria in human prostate cells (PC-3).
Culturing human prostate PC-3 cells for 4, 24, or 72 h in the presence of 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of arachidonic acid metabolism and cholesterol biosynthesis, markedly altered the morphology and reduced the number of mitochondria in the treated cells. Using quantitative electron microscopic morphometry, we documented changes in the number, form, area, matrix density, and integrity of the cristae and limiting membranes of mitochondria in cells cultured with ETYA. The inhibition of cholesterol synthesis or the substitution of ETYA for polyunsaturated fatty acids in the inner membrane may participate in the disruption of the mitochondria, which resembles the morphologic sequelae of oxidative stress. If sufficiently extensive, these changes could contribute to the inhibition of cellular proliferation by ETYA.
Anderson
K M
KM
Department of Medicine, Rush Medical College, Chicago, Illinois 60612.
Seed
T M
TM
Wilson
D E
DE
Harris
J E
JE
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
D001095:Arachidonic Acids; D015117:5,8,11,14-Eicosatetraynoic Acid; D002784:Cholesterol