Effects of n-3 fatty acids during neoplastic progression and comparison of in vitro and in vivo sensitivity of two human tumour cell lines.
Several studies have shown that dietary lipid exerts an effect on carcinogenesis. We report here that progression to malignancy in vitro is associated with changes in the response to fatty acids (FAs). Tumorigenic (THKE) cells were more sensitive to the n-3 FAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) than immortalised (IHKE) cells. The growth of THKE cells was inhibited 25% more than the growth of IHKE cells at 80 microM EPA (P < 0.01) and 35% more at 40 microM DHA (P < 0.001). Furthermore, the results indicate that there is a wide cell type variation in the response to FAs. We found that the in vitro inhibition by FAs correlated with the reduction in the growth rate of the tumour in nude mice fed K85 (55% EPA and 30% DHA). A significant difference in tumour latency was observed for the A427 cell tumour groups (10 days, P < 0.05). Tumours in the animals fed n-3 FA exhibited significantly higher levels of EPA and DHA; the level of arachidonic acid (ARA) was significantly lower in THKE tumours and the level of linoleic acid (LA) was significantly lower in A427 tumours than in controls fed corn oil. The higher sensitivity of the A427 cell line was not explained by higher uptake of EPA/DHA.
Maehle
L
L
Department of Toxicology, National Institute of Occupational Health, Oslo, Norway.
Eilertsen
E
E
Mollerup
S
S
Schønberg
S
S
Krokan
H E
HE
Haugen
A
A
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002461:Cell Line, Transformed; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005227:Fatty Acids / Q000302:isolation & purification / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D011905:Genes, ras; D006801:Humans; D007668:Kidney; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid