title: A small molecule inhibitor of NF-kappaB, dehydroxymethylepoxyquinomicin (DHMEQ), suppresses growth and invasion of nasopharyngeal carcinoma (NPC) cells.
abstract: Despite the demonstrated constitutive activation of NF-kappaB in nasopharyngeal carcinoma (NPC), the therapeutic potential of targeting this pathway has not been investigated. Here, we employed a small molecule inhibitor of NF-kappaB, DHMEQ (which mainly blocks nuclear translocation of activated NF-kappaB) and demonstrated significant inhibition of NPC cell proliferation, migration, invasion, as well as anchorage-independent growth. These antitumor effects were associated with induction of G(2)/M cell cycle arrest and apoptosis, and downregulation of NF-kappaB target genes (EGFR, cyclin D1 and survivin). This first demonstration of therapeutic benefits of NF-kappaB targeting in NPC implicates the importance of targeting this pathway in NPC.
authors: Department of Clinical Oncology, Sir YK Pao Center for Cancer, State Key Laboratory in Oncology in South China, Hong Kong Cancer Institute and Li Ka Shing Institute for Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors: Jason Ho Ting
authors: JH
authors: Wong
authors: Vivian Wai Yan
authors: VW
authors: Lui
authors: Kazuo
authors: K
authors: Umezawa
authors: Yeung
authors: Y
authors: Ho
authors: Elaine Yue Ling
authors: EY
authors: Wong
authors: Margaret Heung Ling
authors: MH
authors: Ng
authors: Suk Hang
authors: SH
authors: Cheng
authors: Chi Man
authors: CM
authors: Tsang
authors: Sai Wah
authors: SW
authors: Tsao
authors: Anthony Tak Cheung
authors: AT
authors: Chan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003512:Cyclohexanones / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009361:Neoplasm Invasiveness; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D001549:Benzamides; D003512:Cyclohexanones; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; C464444:dehydroxymethylepoxyquinomicin; D018799:Intercellular Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9