1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106), a novel potent inhibitor of RNA polymerase, potentiates the cytotoxicity of CDDP in human cancer cells both in vitro and in vivo

  • Authors:
    • Hiromi Kazuno
    • Akio Fujioka
    • Masakazu Fukushima
    • Yusuke Wataya
    • Akira Matsuda
    • Takuma Sasaki
  • View Affiliations

  • Published online on: May 1, 2009     https://doi.org/10.3892/ijo_00000264
  • Pages: 1373-1380
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Abstract

1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106) is a novel antitumor ribonucleoside that inhibits RNA polymerase. In the present study, we investigated the cellular and molecular interactions between TAS-106 and cisplatin (CDDP) in vitro using A549 human lung cancer cells and the in vivo antitumor effect of combined treatment using OCC-1 and LX-1 human tumor xenografts. The treatment effects were determined by evaluating cytotoxicity, the cell cycle distribution, apoptosis induction and the expression of checkpoint-associated proteins. In vitro, the combination of TAS-106 and CDDP synergistically inhibited the growth of A549 cells, as determined using isobologram analysis. TAS-106 potently inhibited the expression of Chk1 protein and the phosphorylation of Chk1 and Chk2. Moreover, based on the inhibition of checkpoint-associated protein, TAS-106 abrogated the CDDP-induced S- and G2M-checkpoints and induced apoptosis in A549 cells. In vivo, TAS-106 alone showed antitumor activity; however, its combination with CDDP significantly enhanced the growth inhibition of OCC-1 and LX-1 tumors. Moreover, combination therapy with TAS-106 and CDDP in the OCC-1 xenograft model resulted in significant life-prolongation. These findings provide a rationale for combination chemotherapy using TAS-106 and CDDP in clinical settings.

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May 2009
Volume 34 Issue 5

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

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Spandidos Publications style
Kazuno H, Fujioka A, Fukushima M, Wataya Y, Matsuda A and Sasaki T: 1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106), a novel potent inhibitor of RNA polymerase, potentiates the cytotoxicity of CDDP in human cancer cells both in vitro and in vivo. Int J Oncol 34: 1373-1380, 2009.
APA
Kazuno, H., Fujioka, A., Fukushima, M., Wataya, Y., Matsuda, A., & Sasaki, T. (2009). 1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106), a novel potent inhibitor of RNA polymerase, potentiates the cytotoxicity of CDDP in human cancer cells both in vitro and in vivo. International Journal of Oncology, 34, 1373-1380. https://doi.org/10.3892/ijo_00000264
MLA
Kazuno, H., Fujioka, A., Fukushima, M., Wataya, Y., Matsuda, A., Sasaki, T."1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106), a novel potent inhibitor of RNA polymerase, potentiates the cytotoxicity of CDDP in human cancer cells both in vitro and in vivo". International Journal of Oncology 34.5 (2009): 1373-1380.
Chicago
Kazuno, H., Fujioka, A., Fukushima, M., Wataya, Y., Matsuda, A., Sasaki, T."1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106), a novel potent inhibitor of RNA polymerase, potentiates the cytotoxicity of CDDP in human cancer cells both in vitro and in vivo". International Journal of Oncology 34, no. 5 (2009): 1373-1380. https://doi.org/10.3892/ijo_00000264