論文 - 詳細
| RRC ID | 42918 |
|---|---|
| 著者 | Sekine T, Takahashi J, Nishishiro M, Arai A, Wakabayashi H, Kurihara T, Kobayashi M, Hashimoto K, Kikuchi H, Katayama T, Kanda Y, Kunii S, Motohashi N, Sakagami H. |
| タイトル | Tumor-specificity and type of cell death induced by trihaloacetylazulenes in human tumor cell lines. |
| ジャーナル | Anticancer Res |
| Abstract |
Twenty trihaloacetylazulene derivatives with one atom of fluorine, chlorine, bromine or iodine was investigated for their tumor-specific cytotoxicity and apoptosis-inducing activity against three human normal cells (gingival fibroblast, HGF; pulp cell, HPC; periodontal ligament fibroblast, HPLF) and four human tumor cell lines (squamous cell carcinoma, HSC-2, HSC-3, HSC-4; promyelocytic leukemia, HL-60). There was no apparent difference in the cytotoxic activity between 2-methoxyazulenes [1a-1e, 2a-2e] and 2-ethoxyazulenes [3a-3e, 4a-4e]. Trichloroacetylazulenes [2a-2e, 4a-4e] generally showed higher cytotoxicity and tumor-specificity (expressed as a TS value) as compared with the corresponding trifluoroacetylazulenes [1a-1e, 3a-3e]. Substitution of chloride [1c, 2c, 3c. 4c], bromide [1d, 2d, 3d, 4d] or iodine [1e, 2e, 3e, 4e] at the C-3 position further enhanced cytotoxic activity against four tumor cell lines, especially HL-60 cells. Among twenty trihaloacetylazulene derivatives, two compounds [2d] and [4c] showed the highest tumor specificity (TS = > 3.5 and > 2.5, respectively). Compounds [2d] and [4c] induced apoptotic cell death characterized by caspase-3, -8 and -9 activation and internucleosomal DNA fragmentation in HL-60 cells. On the other hand, compounds [2d] and [4c] induced autophagic cell death characterized by lower activation of caspases, lack of DNA fragmentation, vacuolization and autophagosome formation detected by acridine orange and LC3-GFP fluorescence, without the decline of the intracellular concentration of three major polyamines in HSC-4 cells. The cytotoxic activity of [4c], but not [2d], was slightly reduced by 3-methyladenine, an inhibitor of autophagy. These results suggest the diversity of cell death type induced in human tumor cell lines by trihaloacetylazulene derivatives. |
| 巻・号 | 27(1A) |
| ページ | 133-43 |
| 公開日 | 2007-1-1 |
| PMID | 17352225 |
| MeSH | Apoptosis / drug effects* Apoptosis / physiology Autophagy / drug effects* Autophagy / physiology Azulenes / chemistry Azulenes / pharmacology* Carcinoma, Squamous Cell / drug therapy* Carcinoma, Squamous Cell / pathology Cell Line Cell Line, Tumor Drug Screening Assays, Antitumor Fibroblasts / cytology Fibroblasts / drug effects HL-60 Cells Humans Hydrocarbons, Halogenated / chemistry Hydrocarbons, Halogenated / pharmacology* Mouth Neoplasms / drug therapy* Mouth Neoplasms / pathology Structure-Activity Relationship |
| IF | 1.994 |
| 引用数 | 60 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | HSC-3(RCB1975) HSC-2(RCB1945) HSC-4(RCB1902) |