Alleviation of the drug-resistant phenotype in idarubicin and cytosine arabinoside double-resistant acute myeloid leukemia cells by indomethacin

Ju Han Song, Seung Hyun Kim, Hyeoung Joon Kim, Seung Yong Hwang, Tae Sung Kim

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Chemoresistance to anticancer drugs is a major issue in the successful treatment of acute myeloid leukemia (AML). In this study, we developed an AML cell line (AML-2/IDAC) that is resistant to treatment with a combination of idarubicin and cytosine arabinoside (Id/AraC) by chronic exposure for more than 3 months. We then investigated the ability of indomethacin to alleviate the chemoresistance of AML-2/IDAC cells. Treatment with indomethacin alone induced growth arrest, but not the death of AML-2/IDAC cells. However, when AML-2/IDAC cells were treated with combinations of indomethacin and Id/AraC, the cell death and apoptosis rate of AML-2/IDAC cells were significantly increased in a dose- and time-dependent manner. The combined treatment with indomethacin and Id/AraC caused the collapse of the mitochondrial membrane potential and was also demonstrated to enhance the activities of caspase-3 and -8 in AML-2/IDAC cells. Furthermore, indomethacin down-regulated expression of the ABCA3 and MRP1 genes, which were over-expressed in AML-2/IDAC cells. Taken together, the results of this study suggest that indomethacin can be used to increase the therapeutic potential against drug-resistant AML when combined with anti-leukemic drugs.

Original languageEnglish
Pages (from-to)931-936
Number of pages6
JournalInternational journal of oncology
Volume32
Issue number4
DOIs
Publication statusPublished - 2008 Apr

Keywords

  • ABC-transporter
  • Acute myeloid leukemia
  • Apoptosis
  • Drug-resistance
  • Indomethacin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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