Effects of fatty acids on liver metastasis of ACL-15 rat colon cancer cells.
The effects of eicosapentaenoic acid [EPA; n-3 polyunsaturated fatty acid (PUFA)], linoleic acid (LA; n-6 PUFA), and palmitic acid (PA; saturated fatty acid) on 1,2-dimethylhydrazine-induced F344 rat colon carcinoma cells (ACL-15) were investigated in vivo and in vitro. The number and size of liver metastatic foci via a superior mesenteric vein injection of ACL-15 cells in F344 rats were significantly inhibited in the EPA-treated group compared with the LA-treated group (p < 0.01); the PA-treated animals and those fed commercial rodent chow (standard diet) demonstrated intermediate values. In a dot immunoblotting assay, vascular cell adhesion molecule 1 expression on ACL-15 cells was downregulated by EPA-ethyl ester treatment and upregulated by LA-ethyl ester treatment compared with the untreated control cells, whereas the expression of matrix metalloproteinase 1 and 2 was not influenced by the fatty acid ethyl esters. In a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, EPA-ethyl ester suppressed ACL-15 cell growth in a schedule-dependent manner, and LA-ethyl ester showed schedule-dependent stimulation. In contrast, PA demonstrated no regulatory effect on cell growth at lower concentrations (< or = 5 mg/ml) but concentration-dependent inhibition at higher concentrations. According to our in vivo cell kinetic study, the difference in tumor growth at the metastatic site was due to different tumor cell proliferation rates; the cell loss rate was not altered. Therefore, the inhibitory effect of liver metastasis on ACL-15 cells by EPA can be explained by a decreased ability of tumor cell adhesion to the capillary bed (low expression of vascular cell adhesion molecule 1) and a lower potential of tumor cell proliferation (low mitotic rate) at the secondary site.
Department of Surgery II, Kansai Medical University, Osaka, Japan.
S
S
Iwamoto
H
H
Senzaki
Y
Y
Kiyozuka
E
E
Ogura
H
H
Takada
K
K
Hioki
A
A
Tsubura
D000818:Animals; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology*; D004041:Dietary Fats / Q000009:adverse effects*; D015118:Eicosapentaenoic Acid / Q000009:adverse effects; D005227:Fatty Acids / Q000009:adverse effects*; D019787:Linoleic Acid / Q000009:adverse effects; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary*; D008297:Male; D019308:Palmitic Acid / Q000009:adverse effects; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured
D004041:Dietary Fats; D005227:Fatty Acids; D019308:Palmitic Acid; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid