Inhibition of ICE-family cysteine proteases rescues murine lymphocytes from lipoxygenase inhibitor-induced apoptosis

Abstract

Two lipophilic derivatives of caffeic acid which inhibit lipoxygenase, caffeic acid phenethyl ester (CAPE) and N,N′-dicyclohexyl-O-(3,4-dihydroxycinnamoyl)-isourea (DCHCU), reduced the proliferative response of murine splenocytes to concanavalin A in vitro. Both CAPE and DCHCU induced apoptosis in murine thymocyte cultures as verified by flow cytometry and by visualisation of DNA with acridine orange staining. CAPE-induced apoptosis was inhibited by z-VAD-fmk, an inhibitor of the interleukin-1β-converting enzyme family of cysteine proteases. We suggest that the lipoxygenase pathway of arachidonic acid metabolism plays a role in regulating lymphocyte responses such as proliferation and apoptosis.