Glucocorticoid receptor-induced down-regulation of MMP-9 by ginseng components, PD and PT contributes to inhibition of the invasive capacity of HT1080 human fibrosarcoma cells.

We examined the effects of the purified ginseng components, panaxadiol (PD) and panaxatriol (PT), on the expression of matrix metalloproteinase-9 (MMP-9) in highly metastatic HT1080 human fibrosarcoma cell line. A significant down-regulation of MMP-9 by PD and PT was detected by Northern blot analysis. However, the expression of MMP-2 was not changed by treatment with PD and PT. Quantitative gelatin based zymography confirmed a markedly reduced expression of MMP-9, but not MMP-2 in the treatment of PD and PT. To investigate whether the reduced level of MMP-9 by PD and PT affects the invasive capacity of HT1080 cells, we conducted an in vitro invasion assay with PD and PT treated cells. The results of the in vitro invasion assay revealed that PD and PT reduced tumor cell invasion through a reconstituted basement membrane in the transwell chamber. Because of the similarity of chemical structure between PD, PT and dexamethasone (Dexa), a synthetic glucocorticoid, we investigated whether the down-regulation of MMP-9 by PD and PT were mediated by the nuclear translocation of glucocorticoid receptor (GR). Increased GR in the nucleus of HT1080 human fibrosarcoma cells treated by PD and PT was detected by immunocytochemistry. Western blot and gel retardation assays confirmed the increase of GR in the nucleus after treatment with PD and PT. These results suggest that GR-induced down-regulation of MMP-9 by PD and PT contributes to reduce the invasive capacity of HT1080 cells.

Polyunsaturated fatty acid composition of the salmon (Salmo salar L.) pineal organ: modification by diet and effect on prostaglandin production.

To examine the influence of dietary polyunsaturated fatty acids (PUFA) on the lipid composition of the pineal organ and its production of prostaglandins, Atlantic salmon were fed diets containing either fish oils rich in long-chain n-3 polyunsaturated fatty acids, or plant oils with high levels of 18:2(n-6) (sunflower oil) or 18:3(n-3) (linseed oil) for 12 weeks. Lipid content and lipid class composition of the pineal organ were not greatly influenced by the type of oil fed to the fish: choline phosphoglycerides were always the predominant lipid class and the proportion of polar lipids exceeded that of neutral lipids. The pattern of PUFA present in total lipid and individual lipid classes was, however, related to that of the dietary oil. The major PUFA in pineal total lipid from all four dietary groups was 22:6(n-3) and the proportion of n-6 PUFA present was highest in lipid from salmon fed sunflower oil. Both PGE and PGF analogues of the 2- and 3-series were detected in pineal homogenates from all dietary groups with the former prostaglandin being the most abundant. The ratio of PGE2/PGE3 was greatest in fish fed sunflower oil and lowest in those fed linseed oil. The results provide further evidence that despite its anatomical location the pineal organ resembles non-neural tissues more than brain in terms of lipid composition and prostaglandin production.

High dietary linoleic acid affects the fatty acid compositions of individual phospholipids from tissues of Atlantic salmon (Salmo salar): association with stress susceptibility and cardiac lesion.

For 16 wk Atlantic salmon (Salmo salar) post-smolts were fed practical-type diets that contained either fish oil (FO) or sunflower oil (SO) as the lipid component. Both diets contained adequate (n-3) polyunsaturated fatty acids (PUFA). All the phospholipids of heart and liver from SO-fed fish had increased levels of 18:2(n-6), 20:2(n-6) and 20:3(n-6); phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) also had increased 20:4(n-6). There was a general decrease in 20:5(n-3) in the phospholipids, reflected in an increase in the 20:4(n-6)/20:5(n-3) ratio, especially in PC and PE. The fatty acid compositions of phospholipids from brain and retina were much less affected by dietary linoleate than those of heart and liver. Fish fed SO developed severe heart lesions that caused thinning of the ventricular wall and muscle necrosis. The fish fed SO also were susceptible to a transportation-induced shock syndrome that caused 30% mortality. These results establish that a diet with a low (n-3)/(n-6) ratio can cause changes in fatty acid metabolism that are deleterious to the health of salmonid fish, especially when subjected to stress.