A novel MEK1/2 inhibitor induces G1/S cell cycle arrest in human fibrosarcoma cells

  • Authors:
    • Taka-Aki Matsui
    • Hiroaki Murata
    • Yoshihiro Sowa
    • Tomoya Sakabe
    • Kazutaka Koto
    • Naoyuki Horie
    • Yoshiro Tsuji
    • Toshiyuki Sakai
    • Toshikazu Kubo
  • View Affiliations

  • Published online on: August 1, 2010     https://doi.org/10.3892/or_00000863
  • Pages: 329-333
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Abstract

Blockade of the ERK pathway has antitumor effects against malignant tumor cells. In this study, we investigated the antitumor activity of JTP-70902, a novel specific MEK inhibitor, against human fibrosarcoma cells in which the ERK pathway is constitutively activated. JTP-70902 was synthesized at Japan Tabacco. Human fibrosarcoma HT1080 cells were cultured. JTP-70902 was added at various concentrations. The number of viable cells was counted employing a trypan blue dye exclusion test. Unsynchronized cells were exposed to JTP-70902 for 24 h. The nuclei were stained with propidium iodide. The DNA content was measured using a FACSCalibur flow cytometer. Protein extraction and Western blot analysis were performed. (1) A dose-dependent inhibition of cell growth was observed at concentrations of 10 nM or more. Forty-eight hours after the treatment, the growth of HT1080 cells was completely inhibited by 200 nM JTP-70902. (2) FACS analysis revealed that a 24-h exposure to JTP-70902 increased the population of G1/S phase cells in a dose-dependent manner. (3) The phosphorylation of ERK was inhibited by JTP-70902. Furthermore, after the treatment with JTP-70902, p21WAF1/CIP1 and p27KIP1 protein expression increased and the phosphorylation of RB was redued. Our results showed that JTP-70902 inhibits cell growth and induces cell cycle arrest in human Ras mutant fibrosarcoma cells. These results indicate that JTP-70902 might be an attractive compound for molecular-targeting chemotherapy for malignant soft tissue tumors with the activation of the Ras-MEK-ERK pathway.

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August 2010
Volume 24 Issue 2

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

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Spandidos Publications style
Matsui T, Murata H, Sowa Y, Sakabe T, Koto K, Horie N, Tsuji Y, Sakai T and Kubo T: A novel MEK1/2 inhibitor induces G1/S cell cycle arrest in human fibrosarcoma cells . Oncol Rep 24: 329-333, 2010
APA
Matsui, T., Murata, H., Sowa, Y., Sakabe, T., Koto, K., Horie, N. ... Kubo, T. (2010). A novel MEK1/2 inhibitor induces G1/S cell cycle arrest in human fibrosarcoma cells . Oncology Reports, 24, 329-333. https://doi.org/10.3892/or_00000863
MLA
Matsui, T., Murata, H., Sowa, Y., Sakabe, T., Koto, K., Horie, N., Tsuji, Y., Sakai, T., Kubo, T."A novel MEK1/2 inhibitor induces G1/S cell cycle arrest in human fibrosarcoma cells ". Oncology Reports 24.2 (2010): 329-333.
Chicago
Matsui, T., Murata, H., Sowa, Y., Sakabe, T., Koto, K., Horie, N., Tsuji, Y., Sakai, T., Kubo, T."A novel MEK1/2 inhibitor induces G1/S cell cycle arrest in human fibrosarcoma cells ". Oncology Reports 24, no. 2 (2010): 329-333. https://doi.org/10.3892/or_00000863