New-type inducers of differentiation of HL-60 leukemia cells suppress c-myc expression.

Abstract

New-type inducers of differentiation of human promyelocytic leukemia cells HL-60, i.e., 4-(5,6,7,8-tetrahydro-5,5,8,8,-tetramethyl-2-naphthalenylcarbamoyl)benzoic acid (Am 80) and (E)-4-[3-(3,5-di-tert-butylphenyl)-3-oxo-1-propenyl]benzoic acid (Ch 55), suppress c-myc expression as all-trans-retinoic acid (RA) does. The decreased level of c-myc expression was detected within 5.sbd.14 h after the start of treatment, and preceded morphological differentiation and functional differentiation measured in terms of nitroblue tetrazolium (NBT) reduction. Treatment of HL-60 cells with 0.1 .mu.M Am 30, Ch 55 or RA for 96 h caused more than 90% suppression of c-myc expression and around 10-fold increase in the percentage of NBT-positive cells.