Abstract A113: Involvement of heme oxygenase-1 (HO-1) in the differentiation of human promyelocytic leukemic cells by DMSO

Abstract

Abstract Heme oxygenase-1 (HO-1), an inducible enzyme with broad tissue expression, is up-regulated in response to hematopoietic stress and preserves vascular homeostasis. We investigated the involvement of HO-1 in the differentiation of HL-60 cells. Dimethylsulfoxide (DMSO), a representative differentiation inducer of HL-60 cells, induced completely decrease HO-1 expression in a time-dependent manner, but increase CD11b, indicating that HO-1 might have negative function in DMSO-induced differentiation of HL-60 cells. Zinc protoporphyrin (ZnPP), a strong inhibitor of HO-1, induced differentiation of HL-60 cells, as evidenced by a marked increase in the expression of CD11b following ZnPP treatment. In contrast, treatment with cobalt protoporphyrin (CoPP), an activator of HO-1, decreased CD11b expression. ZnPP induced down-regulation of HO-1 protein expression in HL-60 cells, while CoPP induced up-regulation. In addition, ZnPP treatment caused a decrease in pRb and cyclin D1 expression and an increase in p21 and p27 expression. These results suggest that down-regulation of HO-1 might be necessary for DMSO-induced HL-60 differentiation. This study provides the first evidence that HO-1 plays an important role in DMSO-induced differentiation of HL-60 cells. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A113.