Polar/apolar compounds induce leukemia cell differentiation by modulating cell-surface potential.
The mechanism of action of polar/apolar inducers of cell differentiation, such as dimethyl sulfoxide and hexamethylene-bisacetamide, is still obscure. In this paper evidence is provided that their effects on murine erythroleukemia cells are modulated by various extracellular cations as a precise function of the cation effects on membrane surface potential. The interfacial effects of the inducers were directly measured on the charged electrode, showing that both dimethyl sulfoxide and hexamethylene-bisacetamide, at the effective concentrations for cell differentiation and within the physiological range of charge density, adsorb at the charged surface and produce a potential shift. A linear correlation was found between this shift and the inducer effects on cell differentiation. Besides offering a different interpretation of the mechanism of action of the inducers, these findings indicate that surface potential has a signaling function. They may also be relevant to cancer treatments based on tumor-cell commitment to terminal differentiation.
Istituto di Patologia Generale, Università di Firenze, Florence, Italy.
A
A
Arcangeli
M
M
Carlà
M R
MR
Del Bene
A
A
Becchetti
E
E
Wanke
M
M
Olivotto
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D007942:Leukemia, Experimental; D008433:Mathematics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008954:Models, Biological; D011188:Potassium / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000081:Acetamides; D000970:Antineoplastic Agents; D002712:Chlorides; D012965:Sodium Chloride; D011189:Potassium Chloride; D012964:Sodium; C014026:hexamethylene bisacetamide; D011188:Potassium; D004121:Dimethyl Sulfoxide