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Effects of a novel NF‐κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on growth, apoptosis, gene expression, and chemosensitivity in head and neck squamous cell carcinoma cell lines
Author(s) -
Ruan Hongying,
Masuda Muneyuki,
Ito Aya,
Umezawa Kazuo,
Nakashima Torahiko,
Yasumatsu Ryuji,
Kuratomi Yuichiro,
Yamamoto Tomoya,
Weinstein I. Bernard,
Komune Shizuo
Publication year - 2006
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.20304
Subject(s) - cyclin d1 , head and neck squamous cell carcinoma , cancer research , apoptosis , cell culture , growth inhibition , cell growth , cisplatin , biology , cell , cell cycle , cancer , head and neck cancer , chemotherapy , biochemistry , genetics
Background. Recent studies provide evidence that the constitutive activation of nuclear factor‐kappa B, NF‐κB 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‐κB 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‐κB protein. Results. DHMEQ showed strong growth inhibitory effects on these two cell lines, with a 50% cell growth inhibition (IC 50 ) concentration of approximately 20 μg/mL. These growth inhibitory effects were associated with inhibition of the NF‐κB 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 μg/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. © 2005 Wiley Periodicals, Inc. Head Neck 27: XXX–XXX, 2005