title: Effects of a novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on growth, apoptosis, gene expression, and chemosensitivity in head and neck squamous cell carcinoma cell lines.
abstract: BACKGROUND
  Recent studies provide evidence that the constitutive activation of nuclear factor-kappa B, NF-kappaB plays a critical role in enhancing the growth of several types of malignancies, including head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  In this study, we examined the effects of a newly synthesized NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on growth, induction of apoptosis, gene expression, and chemosensitivity in two HNSCC cell lines (YCU-H891 and KB), which expressed high levels of nuclear NF-kappaB protein.
  
  
  RESULTS
  DHMEQ showed strong growth inhibitory effects on these two cell lines, with a 50% cell growth inhibition (IC50) concentration of approximately 20 microg/mL. These growth inhibitory effects were associated with inhibition of the NF-kappaB activity. Treatment with DHMEQ induced apoptosis in a dose-dependent manner accounting, at least in part, for the growth inhibition by DHMEQ. DHMEQ strongly inhibited cyclin D1 and vascular endothelial growth factor (VEGF) promoter activity and decreased the levels of cyclin D1 protein and VEGF mRNA in KB cells. In addition, low concentrations of DHMEQ (1.0 or 5.0 microg/mL) synergistically enhanced the cellular sensitivity of YCU-H and KB cells to cisplatin, which is a key chemotherapeutic agent in the treatment of HNSCC.
  
  
  CONCLUSIONS
  These results suggest that DHMEQ may be effective when used alone or in combination with other agents in the treatment of HNSCC.
authors.affiliation: Department of Otorhinolaryngology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Ruan
authors.forename: Muneyuki
authors.initials: M
authors.lastname: Masuda
authors.forename: Aya
authors.initials: A
authors.lastname: Ito
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.forename: Torahiko
authors.initials: T
authors.lastname: Nakashima
authors.forename: Ryuji
authors.initials: R
authors.lastname: Yasumatsu
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kuratomi
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: I Bernard
authors.initials: IB
authors.lastname: Weinstein
authors.forename: Shizuo
authors.initials: S
authors.lastname: Komune
mesh_terms: D017209:Apoptosis; D001549:Benzamides / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D003512:Cyclohexanones / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006258:Head and Neck Neoplasms; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D001549:Benzamides; D003512:Cyclohexanones; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; C464444:dehydroxymethylepoxyquinomicin; D019938:Cyclin D1