1. Academic Validation
  2. A new IkappaB kinase beta inhibitor prevents human breast cancer progression through negative regulation of cell cycle transition

A new IkappaB kinase beta inhibitor prevents human breast cancer progression through negative regulation of cell cycle transition

  • Cancer Res. 2006 Jan 1;66(1):419-26. doi: 10.1158/0008-5472.CAN-05-0741.
Akane Tanaka 1 Susumu Muto Masayo Konno Akiko Itai Hiroshi Matsuda
Affiliations

Affiliation

  • 1 Laboratory of Veterinary Molecular Pathology and Therapeutics, Division of Animal Science, Graduate School, Tokyo University of Agriculture and Technology, Fuchu, Japan.
Abstract

Constitutive nuclear factor-kappaB (NF-kappaB) activity plays a crucial role in the development and progression of lymphoma, leukemia, and some epithelial cancers. Given the contribution of NF-kappaB in carcinogenesis, a novel approach that interferes with its activity might have therapeutic potential against cancers that respond poorly to conventional treatments. Here, we have shown that a new IkappaB kinase beta inhibitor, IMD-0354, suppressed the growth of human breast Cancer cells, MDA-MB-231, HMC1-8, and MCF-7, by arresting cell cycle and inducing Apoptosis. In an electrophoretic mobility shift assay and a reporter assay, IMD-0354 abolished the NF-kappaB activity in MDA-MB-231 cells in a dose-dependent manner. In the cells incubated with IMD-0354, cell cycle arrested at the G0-G1 phase and apoptotic cells were increased. The expression of some cell cycle regulatory molecules and antiapoptotic molecules was suppressed in cells treated with IMD-0354. On the other hand, cyclin-dependent kinase suppressor p27Kip1 was up-regulated by the addition of IMD-0354. Daily administration of IMD-0354 inhibited tumor expansion in immunodeficient mice into which MDA-MB-231 cells were transplanted. These results indicate that NF-kappaB may contribute to cell proliferation through up-regulation of cell cycle progression; accordingly, inhibition of NF-kappaB activity might have a therapeutic ability in the treatment of human breast cancers.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-10172
    99.51%, IKKβ Inhibitor
    IKK