Proteasome inhibitors: their effects on arachidonic acid release from cells in culture and arachidonic acid metabolism in rat liver cells.
BACKGROUND
I have postulated that arachidonic acid release from rat liver cells is associated with cancer chemoprevention. Since it has been reported that inhibition of proteasome activities may prevent cancer, the effects of proteasome inhibitors on arachidonic acid release from cells and on prostaglandin I2 production in rat liver cells were studied.


RESULTS
The proteasome inhibitors, epoxomicin, lactacystin and carbobenzoxy-leucyl-leucyl-leucinal, stimulate the release of arachidonic acid from rat glial, human colon carcinoma, human breast carcinoma and the rat liver cells. They also stimulate basal and induced prostacycin production in the rat liver cells. The stimulated arachidonic acid release and basal prostaglandin I2 production in rat liver cells is inhibited by actinomycin D.


CONCLUSIONS
Stimulation of arachidonic acid release and arachidonic acid metabolism may be associated with some of the biologic effects observed after proteasome inhibition, e.g. prevention of tumor growth, induction of apoptosis, stimulation of bone formation.
Department of Biochemistry, Brandeis University Waltham, MA 02454, USA. llevine@brandeis.edu
Lawrence
L
Levine
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D019073:HT29 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D061988:Proteasome Inhibitors; D051381:Rats
D007976:Leupeptins; D009842:Oligopeptides; D061988:Proteasome Inhibitors; C067713:lactacystin; D016718:Arachidonic Acid; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D000111:Acetylcysteine; C078846:epoxomicin