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.
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.
Ruan
Hong-Ying
HY
Department of Otorhinolaryngology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Masuda
Muneyuki
M
Ito
Aya
A
Umezawa
Kazuo
K
Nakashima
Torahiko
T
Yasumatsu
Ryuji
R
Kuratomi
Yuichiro
Y
Yamamoto
Tomoya
T
Weinstein
I Bernard
IB
Komune
Shizuo
S
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
D001549:Benzamides; D003512:Cyclohexanones; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; C464444:dehydroxymethylepoxyquinomicin; D019938:Cyclin D1