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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

✍ Scribed by Hong-ying Ruan; Muneyuki Masuda; Aya Ito; Kazuo Umezawa; Torahiko Nakashima; Ryuji Yasumatsu; Yuichiro Kuratomi; Tomoya Yamamoto; I. Bernard Weinstein; Shizuo Komune

Publisher
John Wiley and Sons
Year
2006
Tongue
English
Weight
194 KB
Volume
28
Category
Article
ISSN
1043-3074

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✦ Synopsis

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.

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