A small molecule inhibitor of NF-kappaB, dehydroxymethylepoxyquinomicin (DHMEQ), suppresses growth and invasion of nasopharyngeal carcinoma (NPC) cells.
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.
Wong
Jason Ho Ting
JH
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.
Lui
Vivian Wai Yan
VW
Umezawa
Kazuo
K
Ho
Yeung
Y
Wong
Elaine Yue Ling
EY
Ng
Margaret Heung Ling
MH
Cheng
Suk Hang
SH
Tsang
Chi Man
CM
Tsao
Sai Wah
SW
Chan
Anthony Tak Cheung
AT
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
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