論文 - 詳細
RRC ID | 44501 |
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著者 | Ohno M, Ueki J, Sakagami H, Wakabayashi H. |
タイトル | Cytotoxic activity of benzo[b]cyclohept[e][1,4]oxazines. |
ジャーナル | In Vivo |
Abstract |
BACKGROUND:Although numerous articles have dealt with the biological activities of azulenes, studies of benzo[b]cyclohept[e][1,4]oxazines are limited. In the present study, we investigated a total of 14 newly-synthesized benzo[b]cyclohept[e][1,4]oxazines for their growth stimulation at low concentrations (so-called 'hormesis'), cytotoxicity at higher concentrations and apoptosis-inducing activity. MATERIALS AND METHODS:Cytotoxicity of these compounds against human normal gingival fibroblast (HGF) and human oral squamous cell carcinoma cell lines derived from gingival tissue (Ca9-22), was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The tumor specificity (TS) was determined by the ratio of the 50% cytotoxic concentration (CC₅₀) value for HGF cells to that for Ca9-22 cells. Apoptosis induction was evaluated by DNA fragmentation and caspase-3 activation. RESULTS:Compounds 10-(2-methoxyethylamino)benzo[b] cyclohept[e][1,4]oxazine and 10-(3-methoxypropylamino) benzo[b]cyclohept[e][1,4] oxazine, but not other compounds, induced hormesis only in HGF cells. Compound 10-(6-hydroxyhexylamino)benzo[b] cyclohept[e][1,4]oxazine [4] showed the highest cytotoxicity against Ca9-22 cells, followed by 10-(4-hydroxybutylamino) benzo[b]cyclohept[e] [1,4]oxazine and 10-(5-hydroxypentylamino)benzo[b]cyclo-hept[e][1,4]oxazine. Compound [4] did not induce apoptosis markers, but rather induced necrotic cell death (characterized by a smear pattern of DNA fragmentation). CONCLUSION:The present study suggests that the OH group and a certain length of methylene group are necessary for maximal cytotoxicity, and substitution of fluoride in the benzene ring enhances cytotoxicity. |
巻・号 | 27(4) |
ページ | 507-12 |
公開日 | 2013-1-1 |
PII | 27/4/507 |
PMID | 23812221 |
MeSH | Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology Antineoplastic Agents / toxicity Caspase 3 / metabolism Cell Death / drug effects Cell Line Child DNA Fragmentation / drug effects Dose-Response Relationship, Drug Enzyme Activation / drug effects Female Hormesis / drug effects Humans Oxazines / chemistry Oxazines / pharmacology* Oxazines / toxicity |
IF | 1.541 |
引用数 | 2 |
WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL |
リソース情報 | |
ヒト・動物細胞 | Ca9-22(RCB1976) |