DHMEQ, a novel NF-kB inhibitor, induces apoptosis and cell-cycle arrest in human hepatoma cells

  • Authors:
    • Daisuke Nishimura
    • Hiroki Ishikawa
    • Kojiro Matsumoto
    • Hidetaka Shibata
    • Yasuhide Motoyoshi
    • Mariko Fukuta
    • Hiroshi Kawashimo
    • Takashi Goto
    • Naota Taura
    • Tatsuki Ichikawa
    • Keisuke Hamasaki
    • Kazuhiko Nakao
    • Kazuo Umezawa
    • Katsumi Eguchi
  • View Affiliations

  • Published online on: September 1, 2006     https://doi.org/10.3892/ijo.29.3.713
  • Pages: 713-719
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Abstract

Several reports have indicated that nuclear factor-κB (NF-κB) is constitutively activated in a variety of cancer cells including hepatoma cells and plays a key role in their growth and survival. Dehydroxymethylepoxyquinomicin (DHMEQ) derived from the structure of an antibiotic epoxyquinomicin C is a novel NF-κB inhibitor. In the present study, we evaluated the effect of DHMEQ on the NF-κB activity in human hepatoma cells, Huh-7, HepG2 and Hep3B, and the anti-tumor effect of DHMEQ on these cells in vitro and in vivo. DHMEQ inhibited the steady-state transcriptional activity of NF-κB in all hepatoma cells. DHMEQ blocked the constitutive DNA-binding activity and TNF-α-mediated nuclear translocation of NF-κB in Huh-7 cells. DHMEQ (5-20 µg/ml) dose-dependently reduced the viable cell number of all hepatoma cells. DHMEQ (20 µg/ml) induced apoptosis in all hepatoma cells, especially in Hep3B cells, and cell-cycle arrest in Huh-7 and HepG2 cells. These effects were accompanied by downregulation of proteins involved in anti-apoptosis (Bcl-xL, XIAP or c-IAP2) and cell-cycle progression (cyclin D1), and induction of proteins involved in pro-apoptosis (Bax) and cell-cycle retardation (p21Waf1/Cip1), although the degree of changes by DHMEQ was different in each hepatoma cell type. Moreover, intraperitoneal administration of DHMEQ (8 mg/kg) significantly repressed the growth of Huh-7 tumor subcutaneously transplanted into BALB/c nu/nu athymic mice. Our results suggest that DHMEQ could qualify as a candidate for a new chemotherapeutic agent against human hepatoma.

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September 2006
Volume 29 Issue 3

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

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APA
Nishimura, D., Ishikawa, H., Matsumoto, K., Shibata, H., Motoyoshi, Y., Fukuta, M. ... Eguchi, K. (2006). DHMEQ, a novel NF-kB inhibitor, induces apoptosis and cell-cycle arrest in human hepatoma cells. International Journal of Oncology, 29, 713-719. https://doi.org/10.3892/ijo.29.3.713
MLA
Nishimura, D., Ishikawa, H., Matsumoto, K., Shibata, H., Motoyoshi, Y., Fukuta, M., Kawashimo, H., Goto, T., Taura, N., Ichikawa, T., Hamasaki, K., Nakao, K., Umezawa, K., Eguchi, K."DHMEQ, a novel NF-kB inhibitor, induces apoptosis and cell-cycle arrest in human hepatoma cells". International Journal of Oncology 29.3 (2006): 713-719.
Chicago
Nishimura, D., Ishikawa, H., Matsumoto, K., Shibata, H., Motoyoshi, Y., Fukuta, M., Kawashimo, H., Goto, T., Taura, N., Ichikawa, T., Hamasaki, K., Nakao, K., Umezawa, K., Eguchi, K."DHMEQ, a novel NF-kB inhibitor, induces apoptosis and cell-cycle arrest in human hepatoma cells". International Journal of Oncology 29, no. 3 (2006): 713-719. https://doi.org/10.3892/ijo.29.3.713