Interferon-α enhances artemisinin-induced differentiation of HL-60 leukemia cells via a PKCα/ERK pathway

Seung Hyun Kim, Sang Young Chun, Tae Sung Kim

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Interferon-α (IFN-α) has been used in the treatment of several cancers, including chronic myeloid leukemia. Artemisinin, a sesquiterpene lactone endoperoxide that exists in several medicinal plants, is a well known anti-malarial agent. We previously reported that artemisinin by itself caused a relatively low level of HL-60 cell differentiation. In this study, we investigated the effects of IFN-α in combination with artemisinin on cell growth and differentiation in HL-60 leukemia cells. Combination of IFN-α and artemisinin synergistically induced the levels of leukemia cell differentiation, although IFN-α by itself did not affect cell proliferation and differentiation. The increased cell differentiation by IFN-α and artemisinin was significantly suppressed by the inhibitors for protein kinase C (PKC), extracellular signal-regulated kinase (ERK) and jun N-terminal kinase (JNK), but not by the inhibitors for phosphatidylinositol 3-kinase (PI3-K) and p38 mitogen-activated protein kinase (MAPK). Furthermore, co-treatment with IFN-α increased levels of PKCα and phosphorylated ERK. Taken together, these results indicate the enhancement of artemisinin-induced HL-60 cell differentiation by IFN-α through the activation of a PKCα/ERK signaling pathway, and suggest a possible use of IFN-α and artemisinin in the treatment of leukemic diseases.

Original languageEnglish
Pages (from-to)65-72
Number of pages8
JournalEuropean Journal of Pharmacology
Volume587
Issue number1-3
DOIs
Publication statusPublished - 2008 Jun 10

Fingerprint

HL-60 Cells
Extracellular Signal-Regulated MAP Kinases
Protein Kinase C
Interferons
Leukemia
Cell Differentiation
Phosphatidylinositol 3-Kinase
artemisinine
Sesquiterpenes
Antimalarials
p38 Mitogen-Activated Protein Kinases
Lactones
Medicinal Plants
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Phosphotransferases
Cell Proliferation
Growth

Keywords

  • Artemisinin
  • Differentiation
  • Interferon-α
  • Leukemia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Interferon-α enhances artemisinin-induced differentiation of HL-60 leukemia cells via a PKCα/ERK pathway. / Kim, Seung Hyun; Chun, Sang Young; Kim, Tae Sung.

In: European Journal of Pharmacology, Vol. 587, No. 1-3, 10.06.2008, p. 65-72.

Research output: Contribution to journalArticle

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