Establishment of an Arsenic Trioxide—Resistant Human Leukemia Cell Line That Shows Multidrug Resistance

Article

DOI: 10.1532/IJH97.05142

Cite this article as:
Seo, T., Urasaki, Y. & Ueda, T. Int J Hematol (2007) 85: 26. doi:10.1532/IJH97.05142

Abstract

We have established an arsenic trioxide (As2O3)-resistant cell line (K562/AS-3) derived from the human leukemia cell line K562. K562/AS-3 was sequentially cultured with increasing concentrations of As2O3 up to 3.5 µM and then cloned by the limiting dilution method. K562/AS-3 was found to be about 7-fold more resistant to As2O3 than the parent cells (IC50 = 12.9 µM for K562/AS-3 and 1.8 µM for K562), and also showed cross resistance to VP-16 and vincristine. The multidrug resistance—associated protein (MRP1) gene was found to be overexpressed, but the MDR gene was not detected. MRP1 function was evaluated by measuring calcein acetoxymethyl ester (calcein-AM) efflux, and by verifying its inhibition by MK571, a potent MRP inhibitor. In addition, an increase of the total intracellular glutathione content was found in K562/AS-3. The resistance of K562/AS-3 to As2O3 was reversed by the addition of MK571, but not by verapamil. K562/AS-3 may be useful for studying the mechanism of the anticancer effect of As2O3 and how to overcome As2O3-resistance.

Key words

Arsenic trioxideArsenic resistanceK562MRPGlutathione

Copyright information

© The Japanese Society of Hematology 2007

Authors and Affiliations

  1. 1.First Department of Internal MedicineUniversity of FukuiFukuiJapan
  2. 2.Division of Transfusion MedicineFaculty of Medical Sciences, University of FukuiFukuiJapan