Unique action determinants of double acting topoisomerase inhibitor, TAS-103

  • Authors:
    • Ryo Okamoto
    • Hiroshi Takano
    • Takashi Sekikawa
    • Tomotaka Tanaka
    • Masahiro Toyada
    • Kei Ukon
    • Keiji Tanimoto
    • Tsutomu Kumazaki
    • Masahiko Nishiyama
  • View Affiliations

  • Published online on: November 1, 2001     https://doi.org/10.3892/ijo.19.5.921
  • Pages: 921-927
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Abstract

O6-methylguanine-DNA methyltransferase (MGMT), γ-glutamylcysteine synthetase (γ-GCS), and glutathione (GSH) are found to participate in resistance to TAS-103, a topoisomerase I/II inhibitor. In 13 human cancer cell lines, MGMT expression correlated with IC50 for TAS-103, whereas γ-GCS expression inversely correlated with the IC50 value, suggesting MGMT may work to decrease TAS-103 activity but γ-GCS may increase it. A reduced γ-GCS and GSH, and an increased MGMT were associated with the development of resistance in A549 and DLD cells, and γ-GCS inhibition by buthionine sulphoximine increased the TAS-103 resistance, whereas MGMT inhibition by both O6-benzyl-guanine and MGMT-antisense transfection sensitized cells to TAS-103.

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November 2001
Volume 19 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Okamoto R, Takano H, Sekikawa T, Tanaka T, Toyada M, Ukon K, Tanimoto K, Kumazaki T and Nishiyama M: Unique action determinants of double acting topoisomerase inhibitor, TAS-103. Int J Oncol 19: 921-927, 2001
APA
Okamoto, R., Takano, H., Sekikawa, T., Tanaka, T., Toyada, M., Ukon, K. ... Nishiyama, M. (2001). Unique action determinants of double acting topoisomerase inhibitor, TAS-103. International Journal of Oncology, 19, 921-927. https://doi.org/10.3892/ijo.19.5.921
MLA
Okamoto, R., Takano, H., Sekikawa, T., Tanaka, T., Toyada, M., Ukon, K., Tanimoto, K., Kumazaki, T., Nishiyama, M."Unique action determinants of double acting topoisomerase inhibitor, TAS-103". International Journal of Oncology 19.5 (2001): 921-927.
Chicago
Okamoto, R., Takano, H., Sekikawa, T., Tanaka, T., Toyada, M., Ukon, K., Tanimoto, K., Kumazaki, T., Nishiyama, M."Unique action determinants of double acting topoisomerase inhibitor, TAS-103". International Journal of Oncology 19, no. 5 (2001): 921-927. https://doi.org/10.3892/ijo.19.5.921