TY - JOUR
T1 - Enhancing effects of ceramide derivatives on 1,25-dihydroxyvitamin D3-induced differentiation of human HL-60 leukemia cells
AU - Kim, Dong Soo
AU - Kim, Seung Hyun
AU - Song, Ju Han
AU - Chang, Young Tae
AU - Hwang, Seung Yong
AU - Kim, Tae Sung
N1 - Funding Information:
This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (01-PJ10-PG6-01GN16-0005).
PY - 2007/12/14
Y1 - 2007/12/14
N2 - Differentiation-inducing therapy by agents such as 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] 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)2D3 and differentiation-enhancing agents could alleviate the side effects of 1,25-(OH)2D3 and improve the rate of long term survival. In this study, we determined the enhancing activities of ceramide derivatives on 1,25-(OH)2D3-induced differentiation of human myeloid leukemia HL-60 cells. Importantly, some of these derivatives-namely, A2, B3, and H9-enhanced the 1,25-(OH)2D3-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)2D3 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)2D3-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)2D3 may contribute to an effective therapy for AML.
AB - Differentiation-inducing therapy by agents such as 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] 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)2D3 and differentiation-enhancing agents could alleviate the side effects of 1,25-(OH)2D3 and improve the rate of long term survival. In this study, we determined the enhancing activities of ceramide derivatives on 1,25-(OH)2D3-induced differentiation of human myeloid leukemia HL-60 cells. Importantly, some of these derivatives-namely, A2, B3, and H9-enhanced the 1,25-(OH)2D3-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)2D3 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)2D3-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)2D3 may contribute to an effective therapy for AML.
KW - 1,25-Dihydroxyvitamin D
KW - Ceramide library
KW - Differentiation
KW - Leukemia
UR - http://www.scopus.com/inward/record.url?scp=36448975827&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2007.09.035
DO - 10.1016/j.lfs.2007.09.035
M3 - Article
C2 - 18031762
AN - SCOPUS:36448975827
SN - 0024-3205
VL - 81
SP - 1638
EP - 1644
JO - Life Sciences
JF - Life Sciences
IS - 25-26
ER -
