Kinetics of the inhibition of tumour growth in mice by eicosapentaenoic acid-reversal by linoleic acid.
Oral administration of eicosapentaenoic acid (EPA) (2.0 g/kg) by gavage to female NMRI mice bearing the MAC16 colon adenocarcinoma and with weight loss, prevented further loss in body weight and produced a delay in the growth of the tumour. Cell production and loss were determined by the [125I]5-iodo-2'-deoxyuridine method during the stationary and growth phase of the tumour in animals treated with EPA. Tumour stasis appeared to arise from an increase in the rate of cell loss from 38 to 71% without a significant change in the potential doubling time. During the subsequent growth phase the cell loss factor was reduced to 52% and this was combined with a reduced potential doubling time from 32 to 26 hr. The antiproliferative, but not the anticachectic effect of EPA could be reversed by oral administration of pure linoleic acid (LA), (1.9 g/kg) which acted to increase tumour growth by reducing the cell loss factor to 45%. Despite this reversal, incorporation of EPA into tumour cell lipids was not significantly different in animals administered with either EPA alone or combined with LA. This suggests that the antiproliferative effect of EPA in this system may arise from an indirect effect through the blocking of the catabolic effect of the tumour on host adipose tissue, which normally supplies fatty acids essential for tumour growth. This suggests that LA may be required by some tumours to prevent cell loss and that the catabolism of adipose tissue, which accompanies cancer cachexia effectively supplies this fatty acid to the tumour.
Hudson
E A
EA
Pharmaceutical Sciences Institute, Aston University, Birmingham, U.K.
Beck
S A
SA
Tisdale
M J
MJ
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D015118:Eicosapentaenoic Acid / Q000037:antagonists & inhibitors*; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D051379:Mice; D014407:Tumor Cells, Cultured
D005227:Fatty Acids; D008041:Linoleic Acids; D008055:Lipids; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid