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Induction of Myeloid Differentiation of HL-60 Cells with Naphthalene Sulfonamide Calmodulin Antagonists¹

Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710

The naphthalene sulfonamide calmodulin antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide and N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide, both induce limited myeloid differentiation of the human promyelocytic cell line, HL-60. In addition, these inhibitors augment the differentiation observed when HL-60 cells are induced with retinoic acid, dimethyl sulfoxide, or dibutyryl cyclic adenosine monophosphate.

The dose-response curve for HL-60 differentiation was consistent with the published 50% inhibitory dose for inhibition of calmodulin-activated phosphodiesterase and with the calmodulin drug-binding potential of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide and N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide and their less active congeners, N-(6-aminohexyl)-1-naphthalenesulfonamide and N-(4-aminobutyl)-2-naphthalenesulfonamide. These effects, of the naphthalene sulfonamide calmodulin antagonists, are consistent with a regulatory role for calmodulin in cell differentiation, but parallel effects on protein kinase C cannot be excluded.

¹ Supported by a grant from the American Cancer Society CH-301 (M. L. V.) and a grant from the National Cancer Institute CA 35680 (J. N.).

² To whom requests for reprints should be addressed.

Received 2/ 5/85. Revised 11/27/85. Accepted 1/29/86.