title: Antitumor effects of IDN5109 on head and neck squamous cell carcinoma.
abstract: Taxanes, a new class of antitumor drugs, are effective against a large number of human tumors, although there are problems with drug resistance. The novel taxane, IDN5109, is characterized by its high tolerability, antitumor efficacy, ability to overcome multidrug resistance, and oral bioavailabilty. We investigated the cellular response of IDN5109 to head and neck squamous cell carcinoma (HNSCC), and compared the antitumor activity of IDN5109 with that of paclitaxel. This is the first demonstration of antitumor effects of IDN5109 on HNSCC. In in vitro experiments, IDN5109 showed antiproliferative effects against HNSCC cell lines. After treatment with IDN5109, Bcl-2 and Bcl-XL were down-regulated, Bax was up-regulated, and caspase-3 was activated. After treatment with IDN5109, concentrations of both VEGF and IL-8 in the culture supernatant of HNSCC cells decreased. In in vivo experiments, the oral administration of IDN5109 showed antitumor effects against HNSCC tumor xenografts. Immunohistochemistry showed that IDN5109 inhibited tumor angiogenesis and induced apoptosis in HNSCC cells, producing a decreased blood vessel density and increased apoptosis index. On the basis of these results, IDN5109 is useful as a chemotherapeutic agent against HNSCC.
authors.affiliation: Department of Biology and Function in the Head and Neck, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama 236-0004, Japan. t046028d@yokohama-cu.ac.jp
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sano
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsuda
authors.forename: Yukari
authors.initials: Y
authors.lastname: Ishiguro
authors.forename: Goshi
authors.initials: G
authors.lastname: Nishimura
authors.forename: Mariko
authors.initials: M
authors.lastname: Kawakami
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tsukuda
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D017239:Paclitaxel / Q000627:therapeutic use; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; C404743:IDN 5109; D017239:Paclitaxel