ETYA, a pleotropic membrane-active arachidonic acid analogue affects multiple signal transduction pathways in cultured transformed mammalian cells.

摘要: ETYA (5,8,11,14-eicosatetraynoic acid), an arachidonic acid analogue, inhibited DNA synthesis in human transformed U937 (monoblastoid), PC3 (prostate) and A172 (glioblastoma) cells, partially differentiated the lines. The agent is not primarily cytotoxic at concentrations employed, based upon exclusion of trypan blue, continued attachment unchanged release Cr51, reversibility thymidine incorporation after removal ETYA. Leukotriene C4 reversed suppression synthesis, suggesting its modulation by leukotrienes. cells differentiated, as judged a number criteria. increased whole cell microsomal membrane fluidity, intracellular Ca2+ altered distribution activity protein kinase C rapidly downregulated transcription c-myc. Evidence from transmission electron microscopy consistent with oxidative stress including putative lipofuscin bodies, myelin figures disordered mitochondrial cristae matrices was especially evident less so essentially absent cells. A specific 5'-lipoxygenase inhibitor, A63162 proliferation. Some these events are believed to represent components "signal" transduction pathways responsible for reversible inhibition induction partial phenotypic differentiation competent Arachidonic analogues which exert selective effects on physical functional properties membranes may additional class membrane-active agents potential anticancer activity. subset their activities can be duplicated inhibitors 5' lipoxygenase.