Browse by author
Lookup NU author(s): Dr Anastasia Hepburn,
Professor Craig Robson,
Professor Nicola CurtinORCiD
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Antiandrogens are initially effective in controlling prostate cancer (CaP), the second most common cancer in men, but resistance, associated with the loss of androgen-regulated cell cycle control, is a major problem. At present there is no effective treatment for androgen-independent prostate cancer (AIPC). Cellular proliferation is driven by cyclin-dependent kinases (CDKs) with kinase inhibitors (for example, p27) applying the breaks. We present the first investigation of the therapeutic potential of CDK inhibitors, using the guanine-based CDK inhibitor NU2058 (CDK2 IC50 = 17 μM, CDK1 IC50 = 26 μM), in comparison with the antiandrogen bicalutamide (Casodex) in AIPC cells. A panel of AIPC cells was found to be resistant to Casodex-induced growth inhibition, but with the exception of PC3 (GI 50 = 38 μM) and CWR22Rv1 (GI50 = 46 μM) showed similar sensitivity to NU2058 (GI50 = 10-17 μM) compared to androgen-sensitive LNCaP cells (GI50 = 15 μM). In LNCaP cells and their Casodex-resistant derivative, LNCaP-cdxR, growth inhibition by NU2058 was accompanied by a concentration-dependent increase in p27 levels, reduced CDK2 activity and pRb phosphorylation, a decrease in early gene expression and G1 cell cycle phase arrest in both cell lines. In response to Casodex, there were similar observations in LNCaP cells (GI50 = 6 ± 3 μM Casodex) but not in LNCaP-cdxR cells (GI50 = 24 ± 5 μM Casodex). © 2007 Nature Publishing Group All rights reserved.
Author(s): Rigas AC, Robson CN, Curtin NJ
Publication type: Article
Publication status: Published
ISSN (print): 0950-9232
ISSN (electronic): 1476-5594
Publisher: Nature Publishing Group
PubMed id: 17599054
Altmetrics provided by Altmetric