Enhancing effect of indirubin derivatives on 1,25-dihydroxyvitamin D3- and all-trans retinoic acid-induced differentiation of HL-60 leukemia cells

Seung Hyun Kim, Si Wouk Kim, Soo Jeong Choi, Yong Chul Kim, Tae Sung Kim

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The induction of differentiation represents a new and promising approach to cancer therapy, well illustrated by the treatment of acute promyelocytic leukemia (APL) with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or all-trans retinoic acid (ATRA). Using combinations of low, nontoxic concentrations of either 1,25-(OH)2D3 or ATRA and differentiation-enhancing chemicals, adverse effects such as hypercalcemic effects have been ameliorated, and long-term survival has been improved. Indirubin has been demonstrated to exert anti-leukemic effects in cases of chronic myelocytic leukemia. Previously, we synthesized a series of indirubin derivatives and evaluated their anti-proliferative properties against cancer cells. In this study, we determined the enhancing activities of these derivatives on 1,25-(OH)2D3- and ATRA-induced differentiation of human promyelocytic leukemia HL-60 cells. Importantly, some of these derivatives were found to synergistically enhance the differentiation of HL-60 cells in a concentration-dependent manner when coupled with low doses of either 1,25-(OH)2D3 or ATRA. The ability of indirubin derivatives to enhance the differentiation potential of 1,25-(OH)2D3 or ATRA may improve the ultimate outcomes of APL therapy.

Original languageEnglish
Pages (from-to)6752-6758
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number19
DOIs
Publication statusPublished - 2006 Oct 1

Keywords

  • 1,25-Dihydroxyvitamin D
  • All-trans retinoic acid
  • Differentiation
  • Indirubin
  • Leukemia

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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