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 μM dbcAMP with 50 μM 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 μM 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.