Hybrid polar compounds produce a positive shift in the surface dipole potential of self-assembled phospholipid monolayers

Hybrid polar compounds (HPCs) are powerful inducers of terminal differentia tion of various types of tumors, including Friend murine erythroleukemia ce lls (MELCs). They are known to act synergistically with an increase in the extracellular concentration of cations, which causes a positive shift in th e negative value of the ionic surface potential. Two HPCs, hexamethylenebis acetamide (HMBA) and suberoylanilide hydroxamic acid (SAHA), were adsorbed on self-assembled phospholipid monolayers supported on a mercury drop and t he shift in the surface dipole potential chi of the lipid film due to their adsorption was estimated from charge measurements. At their optimal concen trations for inducing MELC terminal differentiation (5 mM for HMBA and 2.6 mu M for SAHA), these HPCs cause a chi shift of about 15-20 mV, positive to ward the hydrocarbon tails, both on neutral phosphatidylcholine films and o n negatively or positively charged phosphatidylserine films. This strongly suggests that the nonspecific effect of HPCs of different structure in indu cing cancer cells to rescue their differentiation program is related to a p ositive chi shift on the extracellular side of the cell membrane. (C) 2000 Elsevier Science B.V. All rights reserved.