| RRC ID |
37835
|
| 著者 |
Narita T, Suga A, Kobayashi M, Hashimoto K, Sakagami H, Motohashi N, Kurihara T, Wakabayashi H.
|
| タイトル |
Tumor-specific cytotoxicity and type of cell death induced by benzo[b]cyclohept[e][1,4]oxazine and 2-aminotropone derivatives.
|
| ジャーナル |
Anticancer Res
|
| Abstract |
A total of twenty benzo[b]cyclohept[e] [1,4]oxazines and their S-analogs, and 2-aminotropone derivatives were investigated for their cytotoxicity against three human normal cells and four tumor cell lines. These compounds showed moderate tumor-specific cytotoxicity. The cytotoxicity was enhanced by bromination at the tropone ring and replacement by formylbenzene. The cytotoxicity of 2-(2-hydroxyanilino) tropone was enhanced by introduction of bromine or isopropyl group to the tropone ring. The presence of a hydroxyl group at ortho or para-position should be necessary for the appearance of cytotoxicity and tumor-specificity. The highly active derivatives, 7-bromo-2-(4-hydroxyanilino)tropone [16] and 4-isopropyl-2-(2-hydroxyanilino)tropone [20], induced internucleosomal DNA fragmentation and caspase-3, -8 and -9 activation in human promyelocytic leukemia HL-60 cells, but only at concentrations twice or four times higher than CC(50) values. These compounds induced no discernible DNA fragmentation, and activated caspases much more weakly in human oral squamous cell carcinoma HSC-2 cells. Both [16] and [20] failed to induce the production of acidic organelles, a marker of autophagy, in contrast to the nutritional starvation. These data demonstrated that 2-aminotropones showed relatively higher tumor-specificity than benzo[b]cyclohept[e] [1,4]oxazine, and that 2-aminotropones induced little or no apoptotic cell death in oral squamous cell carcinoma, in contrast to HL-60 cells.
|
| 巻・号 |
29(4)
|
| ページ |
1123-30
|
| 公開日 |
2009-4-1
|
| PII |
29/4/1123
|
| PMID |
19414354
|
| MeSH |
Carcinoma, Squamous Cell / drug therapy
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / pathology*
Caspases / metabolism
Cell Death / drug effects*
Cells, Cultured
Drug Screening Assays, Antitumor
Enzyme Activation / drug effects
Fibroblasts / drug effects
Humans
Mouth Neoplasms / drug therapy
Mouth Neoplasms / metabolism
Mouth Neoplasms / pathology*
Tropolone / analogs & derivatives*
Tropolone / chemical synthesis
Tropolone / chemistry
Tropolone / pharmacology
|
| IF |
1.994
|
| 引用数 |
12
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HSC-2(RCB1945)
HSC-3(RCB1975)
HSC-4(RCB1902) |
