Enhancing effects of ceramide derivatives on 1,25-dihydroxyvitamin D-3-induced differentiation of human HL-60 leukemia cells
- Authors
- Kim, Dong Soo; Kim, Seung Hyun; Song, Ju Han; Chang, Young-Tae; Hwang, Seung Yong; Kim, Tae Sung
- Issue Date
- Dec-2007
- Publisher
- Elsevier BV
- Keywords
- ceramide library; differentiation; leukemia; 1,25-dihydroxyvitamin D-3
- Citation
- Life Sciences, v.81, no.25-26, pp.1638 - 1644
- Indexed
- SCIE
SCOPUS
- Journal Title
- Life Sciences
- Volume
- 81
- Number
- 25-26
- Start Page
- 1638
- End Page
- 1644
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/43142
- DOI
- 10.1016/j.lfs.2007.09.035
- ISSN
- 0024-3205
- Abstract
- Differentiation-inducing therapy by agents such as 1,25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3] represents a useful approach for the treatment for cancer, including acute myeloid leukemia (AML). Recent studies demonstrated that the combined administration of 1,25-(OH)(2)D-3 and differentiation-enhancing agents could alleviate the side effects of 1,25-(OH)(2)D-3 and improve the rate of long term survival. In this study, we determined the enhancing activities of ceramide derivatives on 1,25-(OH)(2)D-3-induced differentiation of human myeloid leukemia HL-60 cells. Importantly, some of these derivatives-namely, A2, B3, and H9-enhanced the 1,25-(OH)(2)D-3-induced differentiation of HL-60 cells in a concentration-dependent manner. In addition, the morphologic studies using Giemsa staining and flow cytometric analysis demonstrated that the combined treatment of 1,25-(OH)(2)D-3 with one of the three analogues, A2, B3, and H9, directed the HL-60 cells into monocytic lineage, but not into granulocytic lineage. The inhibition studies demonstrated that A2, B3, and H9, enhanced 1,25-(OH)(2)D-3-induced differentiation of HL-60 cells via the PI3-K/PKC/JNK/ERK pathways. The ability of ceramide derivatives to enhance the differentiation-inducing potential of 1,25-(OH)(2)D-3 may contribute to an effective therapy for AML. (C) 2007 Elsevier Inc. All rights reserved.
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