Sun, C. B., Chan, F., Briassouli, P., Linardopoulos, S. (2007) Aurora kinase inhibition downregulates NF-kappa B and sensitises tumour cells to chemotherapeutic agents. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 352 (1). pp. 220-225. ISSN 0006-291X

Full text not available from this repository.

Abstract

We have identified that Aurora-A activates NF-kappaB via IkappaBalpha phosphorylation. Here, we analysed different human tumour cell types for their NF-kappaB activity. We found that there is an association between cell resistance to chemotherapeutic agents and NF-kappaB activation. A549 human lung adenocarcinoma cells and SKOV3 human ovarian cancer cells have high levels of NF-kappaB and are resistant to cytotoxic agents such as adriamycin and VP-16 (etoposide). We also found that in A549 and SKOV3 cells treated with a small molecule inhibitor towards Aurora kinases, the NF-kappaB activity was downregulated and the efficacy of cytotoxic drugs was enhanced. In addition, the transcriptional targets Bcl-XL and Bcl-2 were downregulated. This study provides evidence for a potential mechanism of chemoresistance and may be useful for the enhancement of certain chemotherapeutics regimens.

Item Type:	Article
Authors (ICR Faculty only):	Linardopoulos, Spiros
All Authors:	Sun, C. B., Chan, F., Briassouli, P., Linardopoulos, S.
Uncontrolled Keywords:	Aurora; NF-kappa B; chemotherapeutic agents Susceptibility gene; drosophila aurora; drug-resistance; protein-kinase; cancer; activation; apoptosis; mechanism; cisplatin; family
Research teams:	ICR divisions > Breast Cancer Research > Drug Target Discovery ICR divisions > Cancer Therapeutics > Drug Target Discovery ICR divisions > Breast Cancer Research > Target Discovery & Apoptosis ICR divisions > Cancer Therapeutics > Target Discovery & Apoptosis
Date Deposited:	10 Aug 2007 20:59
Last Modified:	10 Feb 2010 11:48
URI:	http://publications.icr.ac.uk/id/eprint/3124

Actions (login required)

View Item