Effects of hexadecylphosphocholine on protein kinase C and TPA‐induced differentiation of HL60 cells

Several structural analogs of alkylphosphocholine (APC) were studied for their effects on protein kinase C (PKC) and 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA) elicited biochemical and cellular events in HL60 cells. Hexadecylphosphocholine (He‐PC 2 ), the APC prototype, inhibited PKC competitively with respect to phosphatidylserine and noncompetitively with respect to CaCl 2 , both with an apparent K i of about 15 μM. Inhibition of PKC by He‐PC 2 was selective, since cyclic AMP dependent protein kinase and Ca 2+ /calmodulin dependent protein kinase II were relatively unaffected. He‐PC 2 inhibited TPA‐induced depletion of PKC and TPA‐stimulated phosphorylation of cellular proteins in HL60 cells. TPA‐induced differentiation of HL60 cells was also inhibited by He‐PC 2 , and this inhibition was synergistic or additive to the effects of 1‐(5‐isoquinoline‐sulfonyl)‐2‐methylpiperazine (H‐7), a PKC inhibitor. The present findings are consistent with the hypothesis that inhibition of PKC might be related, in part, to the antineoplastic effect of He‐PC 2 and ether lipid analogs such as ET‐18‐OCH 3 (1‐octadecyl‐2‐methyl‐glycero‐3‐phosphocholine).