Synergistic effects of highly unsaturated fatty acid-containing phosphatidyl-ethanolamine on differentiation of human leukemia HL-60 cells by dibutyryl cyclic adenosine monophosphate.

Highly unsaturated fatty acid-containing phospholipid (HUFA-PL) has many nutritional and medical applications. We investigated the effect of HUFA-PL on differentiation of human leukemia HL-60 cells induced by dibutyryl cyclic adenosine monophosphate (dbcAMP). HUFA-containing phosphatidylethanolamine (HUFA-PE), such as salmon testis PE, significantly enhanced dbcAMP-induced cell differentiation. A combined treatment of 200 mM dbcAMP with 50 mM HUFA-PE increased the nitroblue tetrazolium (NBT)-reducing activity, which is an indicator of differentiation, to a level comparable to that in the case of 500 mM dbcAMP treatment. In contrast, HUFA-lyso PE (a monoacyl form) did not exert an enhancing effect on dbcAMP-induced differentiation. The enhancing effect of HUFA-PE was suppressed by a protein kinase C inhibitor, staurosporine, while a protein kinase A inhibitor, H-8, did not suppress the enhancing effect. These findings suggest that HUFA-PE might enhance dbcAMP-induced differentiation through modulation of the protein kinase C signaling pathway in HL-60 cells.