Androgen receptor (AR) is crucial for transcriptional signaling in prostate cancers.
The anti-cancer activity of protein kinase CK2 (formerly called casein kinase 2)-specific small molecule inhibitors have been reported in several cancers including prostate cancers. The orally available CX4945, a potent and selective small molecule inhibitor of CK2, has advanced into human clinical trials and has exhibited strong anti-tumor activity. The inhibition of CK2 leads to a down-regulation of the AR-dependent transcription, but the functional relevance of CX4945 to AR-dependent transcription in AR-positive LNCap cells has not been studied yet. Our observation of inhibitory effects of CX4945 on the expression or phosphorylation levels of CK2α, Akt and anti-apoptotic molecules including IAP family members agreed with a previous study showing the effect of CK2 inhibition in cancer cells. This study also provides novel information on the impact of CX4945 in the inhibition of AR-dependent transcriptional activation in LNCap cells via its down-regulation. Pharmacologic inhibition experiment revealed that CX4945 could exhibit its anti-cancer activity in LNCap cells via the independent inhibitions of AR and Akt-survivin signalings.
Written by:
Ryu BJ, Baek SH, Kim J, Bae SJ, Chang SY, Heo JN, Lee H, Lee SY, Kim SH. Are you the author?
Laboratory of Translational Therapeutics, Pharmacology Research Center, Yuseong-gu, Daejeon 305-600, Republic of Korea.
Reference: Bioorg Med Chem Lett. 2012 Sep 1;22(17):5470-4.
doi: 10.1016/j.bmcl.2012.07.031
PubMed Abstract
PMID: 22832316
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