Dietary supplementation with eicosapentaenoic and docosahexaenoic acid inhibits growth of Morris hepatocarcinoma 3924A in rats: effects on proliferation and apoptosis.
The effect of individual administration of low doses of highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (1 g/kg body weight) on the growth of Morris hepatocarcinoma 3924A transplanted in ACI/T rats was investigated. Both EPA and DHA inhibited growth of the hepatocarcinoma (50% reduction of tumor weight or volume at the 19th day after transplantation for both of the n-3 PUFA groups). EPA treatment reduced the percentage of proliferating tumor cells labeled with BUdR (10-fold), whereas DHA did not. Conversely, DHA supplementation induced a doubling of the number of cells undergoing apoptosis (labeled by TUNEL), whereas EPA treatment was much less effective. Analysis of changes in phospholipid fatty acids in tumor-cell membranes after both treatments with EPA and DHA showed a significant reduction in arachidonic-acid levels. EPA and docosapentaenoic acid (DPA), its elongation product, were increased in the phospholipids from EPA-treated animals. DHA and EPA, but not DPA, were increased in the DHA-treated group. It is concluded from the results of the present study that the anti-tumoral effect of EPA is related mainly to its inhibition of cell proliferation, whereas that of DHA corresponds with its induction of apoptosis. The alterations in fatty-acid composition induced by EPA or DHA appear to be factors underlying their differential actions on cell proliferation and apoptosis.
Calviello
G
G
Institute of General Pathology, Catholic University, Rome, Italy.
Palozza
P
P
Piccioni
E
E
Maggiano
N
N
Frattucci
A
A
Franceschelli
P
P
Bartoli
G M
GM
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D004041:Dietary Fats; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D008114:Liver Neoplasms, Experimental / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D009368:Neoplasm Transplantation; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011912:Rats, Inbred ACI
D004041:Dietary Fats; D008563:Membrane Lipids; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid