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

Hybrid polar compounds (HPCs) are powerful inducers of terminal differentiation of various types of tumors, including Friend murine erythroleukemia cells (MELCs). They are known to act synergistically with an increase in the extracellular concentration of cations, which causes a positive shift in the negative value of the ionic surface potential. Two HPCs, hexamethylenebisacetamide (HMBA) and suberoylanilide hydroxamic acid (SAHA), were adsorbed on self-assembled phospholipid monolayers supported on a mercury drop and the shift in the surface dipole potential chi of the lipid film due to their adsorption was estimated from charge measurements. At their optimal concentrations for inducing MELC terminal differentiation (5 mM for HMBA and 2.6 microM for SAHA), these HPCs cause a chi shift of about 15-20 mV, positive toward the hydrocarbon tails, both on neutral phosphatidylcholine films and on negatively or positively charged phosphatidylserine films. This strongly suggests that the nonspecific effect of HPCs of different structure in inducing cancer cells to rescue their differentiation program is related to a positive chi shift on the extracellular side of the cell membrane.