Eicosanoid inhibitors enhance synergistically the effect of transforming growth factor beta 1 on CCL 64 cell...

The interactions between drugs suppressing the production of arachidonic acid metabolites-eicosanoids and transforming growth factor beta 1 (TGF-beta 1) were investigated using CCL64 cells. These experiments, designed as complete factorial combination of treatments, demonstrated that both esculetin and eicosatetraynoic acid significantly potentiated the inhibitory effect of TGF-beta 1 on [3H]thymidine incorporation. The expression of overadditive effects depended both on the type and concentration of combined factors. These results corresponded with cell cycle analysis data (increased cell number in G1 and decreased cell number in S and G2/M phases) and with the results monitoring cell number following treatment with eicosatetraynoic acid, esculetin, 3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-di methyl propanoic acid (MK-886) and indomethacin. Summarizing, the degree of significance of combined effects supports the hypothesis of synergistic potentiation of TGF-beta 1 effects caused by eicosanoid inhibitors. The results indicate that either the lack of some eicosanoids or a certain type of misbalance in the metabolism of arachidonic acid leading to its abundance might modulate TGF-beta 1 effects on the cell cycle and proliferation in CCL64 cells.