Modulation of the ubiquitin-proteasome proteolytic pathway by eicosapentaenoic acid supplementation in a model of progressive malignancy.
BACKGROUND
A benefit for eicosapentaenoic acid (EPA) supplementation for protein maintenance in cancer patients exists, although specific mechanisms are unknown. As the ubiquitin-proteasome proteolytic (UPP) pathway has been implicated in protein use in malignancy, we determined mRNA levels for UPP components in the liver and muscles from EPA-treated rats bearing the methylcholanthrene (MCA) fibrosarcoma.


METHODS
Rats implanted with MCA tumor were divided into 3 groups on day 13: EPA (5 g/kg per day plus 10 IU vitamin E/g fat), corn oil (5 g/kg per day plus 10 IU vitamin E/g fat), and saline (5 g/kg per day plus 10 IU E/g saline). On day 29, tumor volume (TV) was determined; liver and quadriceps muscles were also excised to determine gene expression of C2, C3, E2(14k), and E3alpha by reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
EPA-treated rats demonstrated a reduced TV of 21% compared with the 28% and 30% TV of corn oil- and saline-treated rats, respectively. Muscle mRNA levels of E2(14k) and E3alpha in EPA-treated animals were decreased compared with corn oil- and saline-treated animals. EPA treatment also decreased hepatic C2, C3, and E2(14k) mRNA levels compared with saline treatment.


CONCLUSIONS
EPA supplement decreased skeletal muscle E2(14k), E3alpha, and hepatic C2 mRNA levels compared with the isocaloric, isonitrogenous corn oil supplement, supporting a treatment-specific effect. The decrease in hepatic C3 and E2(14k) mRNA levels induced by EPA were partly because of caloric benefit and partly attributable to a treatment-specific effect. Additionally, differences in the hepatic and muscle gene expressions of UPP components suggested an organ-specific effect for omega-3 fatty acid activity.
Mikhail
Allen T
AT
Department of Surgery, University of Illinois at Chicago, 60612, USA.
Babcock
Tricia A
TA
Jho
David H
DH
Helton
W Scott
WS
Brodsky
Irwin G
IG
Espat
N Joseph
NJ
D000818:Animals; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D005354:Fibrosarcoma / Q000178:diet therapy / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects; D009928:Organ Specificity; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
D009097:Multienzyme Complexes; D012333:RNA, Messenger; D025801:Ubiquitin; D015118:Eicosapentaenoic Acid; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex