prostaglandin-d2 and arachidonic-acid-5-hydroperoxide

Topics: Arachidonic Acid; Arachidonic Acids; Basophils; Cell Separation; Histamine; Histamine Release; Humans; Leukotrienes; Mast Cells; Peptide Hydrolases; Platelet Activating Factor; Prostaglandin D2; Prostaglandins D; Receptors, IgE; Receptors, Immunologic

The relationship between growth and alterations in arachidonic acid (AA) metabolism in human breast (MCF-7) and colon (SW480) cancer cells was studied. Four different fatty acid preparations were evaluated: a mixture of conjugated linoleic acid (CLA) isomers (c9,t11, t10,c12, c11,t13, and minor amounts of other isomers), the pure c9,t11-CLA isomer, the pure t10,c12-CLA isomer, and linoleic acid (LA) (all at a lipid concentration of 16 microg/mL). 14C-AA uptake into the monoglyceride fraction of MCF-7 cells was significantly increased following 24 h incubation with the CLA mixture (P < 0.05) and c9,t11-CLA (P < 0.02). In contrast to the MCF-7 cells, 14C-AA uptake into the triglyceride fraction of the SW480 cells was increased while uptake into the phospholipids was reduced following treatment with the CLA mixture (P < 0.02) and c9,t11-CLA (P < 0.05). Distribution of 14C-AA among phospholipid classes was altered by CLA treatments in both cell lines. The c9,t11-CLA isomer decreased (P < 0.05) uptake of 14C-AA into phosphatidylcholine while increasing (P < 0.05) uptake into phosphatidylethanolamine in both cell lines. Both the CLA mixture and the t10,c12-CLA isomer increased (P < 0.01) uptake of 14C-AA into phosphatidylserine in the SW480 cells but had no effect on this phospholipid in the MCF-7 cells. Release of 14C-AA derivatives was not altered by CLA treatments but was increased (P < 0.05) by LA in the SW480 cell line. The CLA mixture of isomers and c9,t11-CLA isomer inhibited 14C-AA conversion to 14C-prostaglandin E2 (PGE2) by 20-30% (P < 0.05) while increasing 14C-PGF2alpha by 17-44% relative to controls in both cell lines. LA significantly (P < 0.05) increased 14C-PGD2 by 13-19% in both cell lines and increased 14C-PGE2 by 20% in the SW480 cell line only. LA significantly (P < 0.05) increased 5-hydroperoxyeicosatetraenoate by 27% in the MCF-7 cell line. Lipid peroxidation, as determined by increased levels of 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), was observed following treatment with c9,t11-CLA isomer in both cell lines (P < 0.02) and with t10,c12-CLA isomer in the MCF-7 cell line only (P < 0.05). These data indicate that the growth-promoting effects of LA in the SW480 cell line may be associated with enhanced conversion of AA to PGE2 but that the growth-suppressing effects of CLA isomers in both cell lines may be due to changes in AA distribution among cellular lipids and an altered prostaglandin profile.

Topics: Arachidonic Acid; Breast Neoplasms; Carbon Radioisotopes; Cell Survival; Colonic Neoplasms; Dinoprost; Dinoprostone; Humans; Leukotriene B4; Leukotrienes; Linoleic Acid; Prostaglandin D2; Tumor Cells, Cultured

Prostaglandin (PG) D2 is the major cyclooxygenase metabolite of arachidonic acid released after immunologic stimulation of mast cells. In this report, we demonstrate that this PG is unlike other PGs previously investigated in that it enhances human basophil histamine release at concentrations of 1 to 100 nM. Enhancement is seen when antigen, the phorbol diester, 12-O-tetradecanoylphorbol-13-acetate and ionophore A23187 are used to initiate release and, in preparations of basophils, purified to 51 to 66% of total cell number as well as in preparations of mixed leukocytes. This enhancement is a late or "second stage" phenomenon as defined by the two stages of histamine release and is additive with the enhancement produced by D2O, but not with the enhancement produced by indomethacin or 5-hydroperoxyeicosatetraenoic acid. PGD2 also reverses the inhibition of release produced by drugs and hormones such as dimaprit and PGE2 that activate adenylate cyclase to increase cellular cyclic AMP levels. These data suggest that PGD2 may play an important role in allergic and immunologic reactions and suggest a mechanism by which mast cells and basophils can interact during these reactions.

Topics: Arachidonic Acids; Basophils; Calcimycin; Dimaprit; Dinoprostone; Histamine Release; Humans; Indomethacin; Leukotrienes; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Receptors, Histamine H2; Stimulation, Chemical; Tetradecanoylphorbol Acetate; Thiourea