Anti-tumor activity of dehydroxymethylepoxyquinomicin against human oral squamous cell carcinoma cell lines in vitro and in vivo

被引:23
|
作者
Yasuda, Arisa [1 ]
Kondo, Seiji [1 ]
Nagumo, Tatsuhito [1 ]
Tsukamoto, Hikari [1 ]
Mukudai, Yoshiki [1 ]
Umezawa, Kazuo [2 ]
Shintani, Satoru [1 ]
机构
[1] Showa Univ, Sch Dent, Dept Oral & Maxillofacial Surg, Ohta Ku, Tokyo 1458515, Japan
[2] Keio Univ, Fac Sci & Technol, Dept Appl Chem, Kouhoku Ku, Kanagawa 2230061, Japan
关键词
Nuclear factor-kappa B (NF-kappa B); Dehydroxymethylepoxyquinomicin (DHMEQ); Oral cancer; Apoptosis; Survivin; p65; p50; Anticancer drug; NF-KAPPA-B; CANCER; INHIBITOR; APOPTOSIS; INDUCTION; MACROPHAGES; CAPACITY; ENHANCE;
D O I
10.1016/j.oraloncology.2011.03.001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Several reports have indicated that nuclear factor-kappa B (NF-kappa B) is constitutively activated in a variety of cancer cells including human oral squamous carcinoma cells, and play a key role in their growth and survival. Recent studies report that NF-kappa B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), inhibits proliferation and induces apoptosis in prostate cancer cell lines. However this anti-tumor effects are still unknown in end human oral squamous carcinoma cells. In the present study, we investigated the effects of DHMEQ on oral squamous carcinoma cell (OSCC) lines in vitro and in vivo. Human OSCC cell lines (HSC-3, SAS) were treated with DHMEQ and examined for cell viability by MTT assay, cell cycle distribution by flow-cytometry, apoptosis by TUNEL assay, and protein expression by western blotting, respectively. In vivo activities were also investigated in a mouse xenograft model. DHMEQ inhibited growth of two OSCC cell lines in a dose-dependent manner measured by MTT assay. A flow cytometric analysis demonstrated that treatment with DHMEQ induced accumulation in sub-G1 phase. TUNEL assay showed that DHMEQ induced DNA fragmentation. Protein expression by western blotting analysis revealed that DHMEQ induced nuclear down regulation of Survivin, cIAP-1, and cIAP-2. In nude mice, DHMEQ inhibited growth of OSCC without major toxic side effects. The present results demonstrated that administration of DHMEQ is suggested to be a novel anti-tumor approach to the treatment of OSCC. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:334 / 339
页数:6
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