Inhibitory effect of nitric oxide on chemically induced differentiation ofhuman leukemic K562 cells

The effect of nitric oxide (NO) was investigated in the human K562 cell lin e during chemically induced erythroid differentiation. Butyric acid (BA) an d the anthracycline antitumour drugs aclarubicin (ACLA) and doxorubicin (DO X) were used as differentiating agents. In all cases, cell hemoglobinizatio n was dose dependently inhibited by NO donors such as sodium nitroprusside (SNP). A 50% inhibition of cell differentiation was obtained with 25 mu M S NP, which generated less than 2 mu M nitrite in 3-day culture media. Increa sing SNP concentrations led to higher nitrite accumulation (up to 12 mu M w ith 1 mM SNP) and total inhibition of cell hemoglobinization, but did not h ave a significant effect on cell proliferation. As shown by Northern blotti ng, high concentrations of SNP (1 mM) reduced the expression of gamma-globi n and porphobilinogen deaminase, but did not change GATA-1 and NF-E2 mRNA l evels in ACLA- and BA-treated cells. In contrast, hemin-induced erythroid d ifferentiation was not affected by the presence of NO donors. Altogether, t hese results show that NO is able to inhibit cell differentiation induced b y some (ACLA, DOX, BA), but not all (hemin), agents. The inhibitory effect of NO seems to take place downstream of the regulation of erythroid gene ex pression. (C) 1999 Elsevier Science Inc.