title: Anti-tumor activity of dehydroxymethylepoxyquinomicin against human oral squamous cell carcinoma cell lines in vitro and in vivo.
abstract: Several reports have indicated that nuclear factor-kappa B (NF-κB) 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-κB 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.
authors: Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta-ku, Tokyo 145-8515, Japan. a.r.i@dent.showa-u.ac.jp
authors: Arisa
authors: A
authors: Yasuda
authors: Seiji
authors: S
authors: Kondo
authors: Tatsuhito
authors: T
authors: Nagumo
authors: Hikari
authors: H
authors: Tsukamoto
authors: Yoshiki
authors: Y
authors: Mukudai
authors: Kazuo
authors: K
authors: Umezawa
authors: Satoru
authors: S
authors: Shintani
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D003512:Cyclohexanones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D051379:Mice; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D003512:Cyclohexanones; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; C464444:dehydroxymethylepoxyquinomicin