Cancer Letters
Volume 220, Issue 1 , Pages 49-55, 18 March 2005

The combination of Jun N-terminal kinase inhibitor and TNP-470 blocks carcinosarcoma-induced endothelial cell tube formation in a synergistic manner

  • Shin-ichiro Miura

      Affiliations

    • Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan
    • Corresponding Author InformationCorresponding author. Tel.: +81-92-801-1011; fax: +81-91-865-2692.
    • ,
  • Makoto Emoto

      Affiliations

    • Department of Obstetrics and Gynecology, Fukuoka University School of Medicine, Fukuoka, Japan
    • ,
  • Yoshino Matsuo

      Affiliations

    • Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan
    • ,
  • Tatsuhiko Kawarabayashi

      Affiliations

    • Department of Obstetrics and Gynecology, Fukuoka University School of Medicine, Fukuoka, Japan
    • ,
  • Keijiro Saku

      Affiliations

    • Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan

Received 13 February 2004; received in revised form 21 June 2004; accepted 25 June 2004.

Abstract 

We assessed the usefulness of Jun N-terminal kinase inhibitor (JNK-I) as an anti-angiogenic agent against a human uterine carcinosarcoma cell line (FU-MMT-1). JNK-I blocked FU-MMT-1-induced human arterial endothelial cell (HAEC) tube formation in an in vitro co-culture model. Cell proliferation of FU-MMT-1 or HAEC was inhibited by JNK-I. In addition, JNK-I blocked matrix metalloproteinase production but not vascular endothelial growth factor (VEGF) secretion in HAECs. Although low concentrations of JNK-I or TNP-470, an anti-cancer agent, did not separately block FU-MMT-1-induced tube formation, such tube formation was blocked by the combination of low concentrations of JNK-I and TNP-470 because TNP-470 blocked VEGF production, suggesting that JNK-I and TNP-470 had a synergistic effect and might be effective in patients with carcinosarcoma.

Keywords: Jun N-terminal kinase inhibitor, TNP-470, FU-MMT-1, Matrix metalloproteinases

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PII: S0304-3835(04)00509-9

doi:10.1016/j.canlet.2004.06.048

Cancer Letters
Volume 220, Issue 1 , Pages 49-55, 18 March 2005

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