Isolation and characterization of arsenite-resistant human epidermoid carcinoma KB cells

  • Authors:
    • Tokushi Tachiwada
    • Zhe-Sheng Chen
    • Xiao-Fang Che
    • Mitsugu Matsumoto
    • Misako Haraguchi
    • Takenari Gotanda
    • Tomoyuki Sumizawa
    • Tatsuhiko Furukawa
    • Kenryu Nishiyama
    • Naohiko Seki
    • Masatatsu Yamamoto
    • Masayuki Nakagawa
    • Shin-Ichi Akiyama
  • View Affiliations

  • Published online on: September 1, 2007     https://doi.org/10.3892/or.18.3.721
  • Pages: 721-727
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Abstract

Arsenic trioxide (As2O3) has been used with success in the treatment of acute promyelocytic leukemia. However, resistance to arsenite agents reduces their efficacy. We have isolated arsenite-resistant human epidermoid carcinoma KB cells, termed KAS. KAS cells were resistant to sodium arsenite (22-fold) and showed a reduced accumulation of arsenite as a result of an active efflux mechanism. Further analysis indicated that resistance of KAS cells extended to other drugs including cisplatin (17-fold), antimony potassium tartrate (11-fold) and doxorubicin (27-fold). Although increased expression of multidrug resistance protein 1 (MRP1) in KAS cells was confirmed by quantitative RT-PCR and immunoblot analysis, specific inhibitors of MRP1 did not completely eliminate arsenite resistance. The level of glutathione (GSH) in KAS cells was 3-fold higher than that in KB-3-1 cells, and the inhibition of GSH synthesis by buthionine sulfoximine (BSO) considerably increased the cytotoxic effect of arsenite on KAS cells. A pyridine analog, 2-[4-(diphenylmethyl)-1-piperazinyl ethyl 5-(trans-4,6-dimethyl-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridine-carboxylate P oxide (PAK-104P), partially reversed the arsenite resistance and increased the arsenite accumulation in KAS cells. We suggest that the increased level of GSH is involved in arsenite resistance and an as yet unidentified arsenite transporter is expressed in the arsenite-resistant KAS cells.

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September 2007
Volume 18 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Tachiwada T, Chen Z, Che X, Matsumoto M, Haraguchi M, Gotanda T, Sumizawa T, Furukawa T, Nishiyama K, Seki N, Seki N, et al: Isolation and characterization of arsenite-resistant human epidermoid carcinoma KB cells. Oncol Rep 18: 721-727, 2007
APA
Tachiwada, T., Chen, Z., Che, X., Matsumoto, M., Haraguchi, M., Gotanda, T. ... Akiyama, S. (2007). Isolation and characterization of arsenite-resistant human epidermoid carcinoma KB cells. Oncology Reports, 18, 721-727. https://doi.org/10.3892/or.18.3.721
MLA
Tachiwada, T., Chen, Z., Che, X., Matsumoto, M., Haraguchi, M., Gotanda, T., Sumizawa, T., Furukawa, T., Nishiyama, K., Seki, N., Yamamoto, M., Nakagawa, M., Akiyama, S."Isolation and characterization of arsenite-resistant human epidermoid carcinoma KB cells". Oncology Reports 18.3 (2007): 721-727.
Chicago
Tachiwada, T., Chen, Z., Che, X., Matsumoto, M., Haraguchi, M., Gotanda, T., Sumizawa, T., Furukawa, T., Nishiyama, K., Seki, N., Yamamoto, M., Nakagawa, M., Akiyama, S."Isolation and characterization of arsenite-resistant human epidermoid carcinoma KB cells". Oncology Reports 18, no. 3 (2007): 721-727. https://doi.org/10.3892/or.18.3.721