σ2 Receptors regulate changes in sphingolipid levels in breast tumor cells

Abstract σ 2 Receptors induce apoptosis in various cell types. The sphingolipid, ceramide as well as the sphingoid bases are involved in cell proliferation. Sphingolipids of MCF-7/Adr- and T47D breast tumor cells were metabolically radiolabeled. The σ 2 receptor agonists (+)-1 R ,5 R - E -8-(3,4-dichlorobenzylidene)-5-(3-hydroxyphenyl)-2-methylmorphan-7-one (CB-184) and 1 S ,2 R -(−)- cis - N -[2-(3,4-dichlorophenyl)ethyl]- N -methyl-2-(1-pyrrolidinyl)-cyclohexylamine (BD737) caused dose-dependent increases in [ 3 H]ceramide, with concomitant decreases in [ 3 H]sphingomyelin. Both effects were attenuated by the novel σ 2 receptor antagonist, N -phenethylpiperidine oxalate (AC927). σ 2 Receptors may produce effects on cell growth and apoptosis by regulating the sphingolipid pathway.