title: IKK inhibitor suppresses epithelial-mesenchymal transition and induces cell death in prostate cancer.
abstract: IκB kinase (IKK)/nuclear factor κB (NF-κB) pathway activation is a key event in the acquisition of invasive and metastatic capacities in prostate cancer. A potent small-molecule compound, BMS-345541, was identified as a highly selective IKKα and IKKβ inhibitor to inhibit kinase activity. This study explored the effect of IKK inhibitor on epithelial-mesenchymal transition (EMT), apoptosis and metastasis in prostate cancer. Here, we demonstrate the role of IKK inhibitor reducing proliferation and inducing apoptosis in PC-3 cells. Furthermore, BMS345541 inhibited IκBα phosphorylation and nuclear level of NF-κB/p65 in PC-3 cells. We also observed downregulation of the N-cadherin, Snail, Slug and Twist protein in a dose-dependent manner. BMS‑345541 induced upregulation of the epithelial marker E-cadherin and phosphorylated NDRG1 at protein level. Moreover, BMS‑345541 reduced invasion and metastasis of PC-3 cells in vitro. In conclusion, IKK has a key role in both EMT and apoptosis of prostate cancer. IKK inhibitor can reverse EMT and induce cell death in PCa cells. IKK was identified as a potential target structure for future therapeutic intervention in PCa.
authors.affiliation: Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ping
authors.affiliation: Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Feiya
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Mingshuai
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Yinong
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Nianzeng
authors.initials: N
authors.lastname: Xing
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors; D007093:Imidazoles / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C471109:4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline; D000970:Antineoplastic Agents; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011810:Quinoxalines; D051550:I-kappa B Kinase