RRC ID 44501
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)