Enhancing effects of ceramide derivatives on 1,25-dihydroxyvitamin D(3)-induced differentiation of human HL-60 leukemia cells

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-enh...

Full description

Saved in:
Bibliographic Details
Published in:Life sciences (1973) 2007-12, Vol.81 (25-26), p.1638
Main Authors: Kim, Dong Soo, Kim, Seung Hyun, Song, Ju Han, Chang, Young-Tae, Hwang, Seung Yong, Kim, Tae Sung
Format: Article
Language:English
Subjects:
Antigens, Surface - chemistry
Antineoplastic Agents - pharmacology
Cell Differentiation - drug effects
Ceramides - chemical synthesis
Ceramides - pharmacology
Drug Synergism
Flow Cytometry
HL-60 Cells - cytology
HL-60 Cells - drug effects
Humans
Mitogen-Activated Protein Kinases - metabolism
Monocytes - chemistry
Monocytes - cytology
Vitamin D - analogs & derivatives
Vitamin D - pharmacology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0024-3205