title: Anti-androgen receptor activity of apoptotic CK2 inhibitor CX4945 in human prostate cancer LNCap cells.
abstract: 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.
authors: Laboratory of Translational Therapeutics, Pharmacology Research Center, Yuseong-gu, Daejeon 305-600, Republic of Korea.
authors: Byung Jun
authors: BJ
authors: Ryu
authors: Seung-hwa
authors: SH
authors: Baek
authors: Jiyeon
authors: J
authors: Kim
authors: Su Jung
authors: SJ
authors: Bae
authors: Sung-Youn
authors: SY
authors: Chang
authors: Jung-Nyoung
authors: JN
authors: Heo
authors: Hyuk
authors: H
authors: Lee
authors: Sang Yeol
authors: SY
authors: Lee
authors: Seong Hwan
authors: SH
authors: Kim
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology*; D010619:Phenazines; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D009287:Naphthyridines; D010619:Phenazines; D011944:Receptors, Androgen; C555142:silmitasertib; D047390:Casein Kinase II