Apoptosis-inducing natural products found in utero during murine pregnancy

Background: Hormones, lipids, Vitamins and other biologically active smalt molecules can be removed from animal tissues by extraction with organic sol vents. These compounds can have dramatic effects on cultured cells and the characterization of such compounds can lead to the discovery of new functio ns for known molecules, or even to the discovery of previously unknown comp ounds. Results: Organic-soluble compounds in 17.5-day-old mouse embryos were remov ed with tert-butylmethylether and found to induce apoptosis in T-antigen-tr ansformed Jurkat T cells. These embryonic extracts were fractionated and th eir apoptosis-inducing components were identified as a mixture of polyunsat urated fatty acids, including arachidonic, docosatetraenoic and docosahexae noic acids. Docosatetraenoic acid was the most potent apoptosis inducer wit h an effective dose (ED50) of 30 mu M. Conclusions: A family of polyunsaturated fatty acids is shown to be abundan t in utero during pregnancy. Members of this family are able to induce clea vage of poly(ADP)ribose polymerase, and ultimately to induce apoptosis, in T-antigen-transformed Jurkat T cells. Free radical scavengers, including ph enol and benzyl alcohol, block the apoptosis-inducing properties of these p olyunsaturated fatty acids; this is consistent with a lipid peroxidation me chanism involving formation of hydroperoxy fatty acids.