Eicosapentaenoic acid and sulphur substituted fatty acid analogues inhibit the proliferation of human breast cancer cells in culture.

Numerous studies have shown dietary fatty acids to influence the progression of several types of cancers. The purpose of the present investigation was to examine the influence of various types of fatty acids, including omega-3 fatty acids and a new class of hypolipidemic peroxisome proliferating fatty acid analogues, namely the 3-thia fatty acids, on MCF-7 human breast cancer cell growth. 3-thia fatty acids represent non-beta-oxidizable fatty acid analogues in which a sulphur atom substitutes for the beta-methylene group (3-position) in the saturated and unsaturated fatty acids. The effects of increasing concentrations of palmitic acid, tetradecylthioacetic acid (a 3-thia fatty acid), eicosapentaenoic acid, docosahexaenoic acid, and two 3-thia polyunsaturated fatty acids on the proliferation of MCF-7 cells, maintained in serum-free culture, were studied. At the highest concentration of fatty acid used (64 microM) tetradecylthioacetic acid was found to be the most effective of all fatty acids tested in inhibiting cell growth, whilst palmitic acid and docosahexaenoic acid had no significant effect on cell growth. Thus, of the two dietary polyunsaturated omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid, only eicosapentaenoic acid possesses an inhibitory effect on the proliferation of MCF-7 cells. In all cases the inhibitory effect of the fatty acid was found to be reversible. Tetradecylthioacetic acid has been shown to be a potent peroxisome proliferator. It was, therefore, hypothesized that tetradecylthioacetic acid may inhibit the human MCF-7 cell growth by increasing the level of oxidative stress within the cell. However, use of agents which modify the cell's protective apparatus against oxidative stress had no influence on the inhibitory effect of tetradecylthioacetic acid. These experiments indicate that tetradecylthioacetic acid inhibits cell growth by mechanisms which may be independent of oxidative status.

Role of prostaglandins and histamine in hyperemic response to superficial and deep gastric mucosal injury and H+ back-diffusion in cats.

This study was undertaken to examine the role of prostaglandins and histamine in the hyperemic response to gastric mucosal damage followed by H+ back-diffusion. Cat stomachs were exposed to 2 mol/liter NaCl for 10 min followed by luminal perfusion at pH 1. Hypertonic saline caused extensive (microscopic) damage to the surface epithelium, increased gastric mucosal blood flow, and increased release of histamine, PGE2, and 6-keto PGF1 alpha (prostacyclin) into portal venous blood. The effect of indomethacin and histamine blockers (H1 + H2) on the hyperemic response to acid back-diffusion was related to the depth of the mucosal injury and the region of the stomach. In the corpus, indomethacin enhanced mucosal injury. In areas with superficial damage, the hyperemia was inhibited by indomethacin and antihistamines and eliminated by the combination of both. In corpus areas with indomethacin-induced deep lesions, the blood flow was very high, and this hyperemia was partly inhibited by antihistamines. In the antrum the hyperemic response was reduced by antihistamines. Indomethacin increased the release of histamine into portal venous blood (baseline recordings) and reduced basal gastric mucosal blood flow.

Hormonal control of proteins synthesized and secreted by guinea-pig endometrium.

The amounts of protein synthesized and secreted (as indicated by [3H]leucine incorporation) by guinea-pig endometrium cultured for 24 h increased 2.1-fold between days 7 and 15 of the oestrous cycle. This increase did not occur if the guinea-pigs were pregnant. In ovariectomized guinea-pigs, oestradiol acting on a progesterone-primed uterus was the optimum stimulus for the maximum increase in endometrial protein synthesis and secretion. The two main proteins synthesized and secreted by day-15 guinea-pig endometrium had molecular masses of 99.8 and 192.1 kDa as determined on Sephacryl S-200HR. The production of the 99.8 kDa protein increased 5.2-fold between days 7 and 15 of the cycle. The 192.1 kDa protein was not detected in secretions produced by day 7 endometrium, and the 99.8 and 192.1 kDa proteins were not detected in secretions produced by day-15 pregnant endometrium. In ovariectomized guinea-pigs, progesterone did not stimulate the synthesis of secreted proteins of molecular masses above 77 kDa. Oestradiol stimulated the synthesis of secreted proteins with molecular masses of 87.8 and 192.1 kDa. However, oestradiol acting on a progesterone-primed uterus stimulated the synthesis of the secreted proteins with molecular masses of 99.8 and 192.1 kDa, which indicates that this combination of steroid hormones may be responsible for the increase in production of these two proteins by the day-15, nonpregnant guinea-pig endometrium. This stimulation by ovarian steroids of the synthesis and secretion of the 99.8 and 192.1 kDa proteins by the guinea-pig endometrium is apparently inhibited during early pregnancy.

Proteins synthesized and secreted by the guinea-pig conceptus during early pregnancy in relation to corpus luteal maintenance.

Guinea-pig conceptuses obtained on Day 15 of pregnancy were cultured for 24 h in the presence of [3H]leucine. Proteins present in the culture medium were purified by dialysis, desalted, and subjected to analysis by gel filtration chromatography, ion-exchange chromatography, and polyacrylamide gel electrophoresis. The major non-radioactive protein present co-chromatographed with serum albumin. Fresh protein synthesis occurred as indicated by the incorporation of [3H]leucine, and the proteins produced were acidic in nature. Many radioactive proteins in relatively similar amounts were produced, with protein of molecular weights 28.8 and 98.2 kDa (as determined on Sephacryl S-300HR) and of molecular weights 8.4 and 14.7 kDa (as determined on Sephadex G-75SF) being synthesized in marginally greater quantities. Consequently, from the profile of proteins synthesized and secreted, no obvious candidate emerged as the anti-luteolytic factor synthesized and secreted by the guinea-pig conceptus during early pregnancy which inhibits endometrial PGF2 alpha synthesis and maintains corpus luteal function.