Nargenicin enhances 1,25-dihydroxyvitamin D3- and all-trans retinoic acid-induced leukemia cell differentiation via PKCβI/MAPK pathways

Seung Hyun Kim, Jin Cheol Yoo, Tae Sung Kim

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

A major goal in the treatment of acute myeloid leukemia (AML) is to achieve terminal differentiation and prevent drug resistance and side effects. Combined treatment with low doses of ATRA or 1,25-(OH)2D3 that do not induce toxicity with another drug is one useful strategy for the treatment of AML. Actinomycetes are the well known sources of antibiotics and bioactive molecules. Previously, we isolated nargenicin from the culture broth of an actinomycete isolate, Nocardia sp. CS682. In this study, we evaluated the effects of nargenicin on cellular differentiation in a human myeloid leukemia HL-60 cell system. Nargenicin inhibited cell proliferation and induced HL-60 cell differentiation when administered in combination with 1,25-(OH)2D3 or ATRA. In addition, western blot analyses and kinase inhibitor studies demonstrated that nargenicin primarily enhanced leukemia cell differentiation via PKCβ1/MAPK pathways. The results of this study indicate that nargenicin has the ability to induce differentiation and suggest that it may be useful for the treatment of neoplastic diseases.

Original languageEnglish
Pages (from-to)1694-1701
Number of pages8
JournalBiochemical Pharmacology
Volume77
Issue number11
DOIs
Publication statusPublished - 2009 Jun 1

Keywords

  • 1,25-Dihydroxyvitamin D
  • All-trans retinoic acid
  • Cell differentiation
  • Mitogen-activated protein kinase
  • Nargenicin
  • Protein kinase C

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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