| RRC ID |
43317
|
| 著者 |
Motani K, Tabata K, Kimura Y, Okano S, Shibata Y, Abiko Y, Nagai H, Akihisa T, Suzuki T.
|
| タイトル |
Proteomic analysis of apoptosis induced by xanthoangelol, a major constituent of Angelica keiskei, in neuroblastoma.
|
| ジャーナル |
Biol Pharm Bull
|
| Abstract |
Neuroblastoma is the most common solid tumor in children. Despite aggressive chemotherapy, the prognosis of patients with advanced neuroblastoma is still very poor. Our recent study showed that xanthoangelol, a major chalcone constituent of the stem exudates of Angelica keiskei, induced caspase-3-dependent apoptosis in neuroblastoma cells. However, details of the mechanism underlying its apoptotic action are still unclear. Here we show that xanthoangelol triggers oxidative stress by generation of reactive oxygen species and induces apoptosis through release of cytochrome c and activation of caspase-9 in IMR-32 cells. Pretreatment with an antioxidant, vitamin E, prevented the increase of reactive oxygen species and apoptosis induced by xanthoangelol. Proteomic analysis using 2-dimensional electrophoresis and MALDI-TOF-MS revealed that DJ-1 protein was involved in xanthoangelol-induced apoptosis. DJ-1 responded to its oxidative stress status by being oxidized itself. Furthermore, DJ-1 was down-regulated by xanthoangelol, leading to loss of antioxidant function and acceleration of apoptosis. We also show that xanthoangelol has a cytotoxic effect on drug-resistant LA-N-1 and NB-39 cells as well as drug-sensitive IMR-32 and SK-N-SH cells. These findings suggest that xanthoangelol induces apoptosis by increasing reactive oxygen species and targeting DJ-1, and such mechanism may be an effective therapeutic approach for advanced neuroblastoma.
|
| 巻・号 |
31(4)
|
| ページ |
618-26
|
| 公開日 |
2008-4-1
|
| DOI |
10.1248/bpb.31.618
|
| PII |
JST.JSTAGE/bpb/31.618
|
| PMID |
18379052
|
| MeSH |
Angelica / chemistry*
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects*
Benzimidazoles
Blotting, Western
Brain Neoplasms / drug therapy*
Brain Neoplasms / pathology
Cell Line, Tumor
Chalcone / analogs & derivatives*
Chalcone / pharmacology
Down-Regulation / drug effects
Drug Resistance, Neoplasm
Electrophoresis, Gel, Two-Dimensional
Fluorescent Dyes
Humans
Neoplasm Proteins / biosynthesis
Neoplasm Proteins / genetics
Neuroblastoma / drug therapy*
Neuroblastoma / pathology
Plant Stems / chemistry
Proteomics*
RNA, Small Interfering / pharmacology
Reactive Oxygen Species / metabolism
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Subcellular Fractions / metabolism
Tetrazolium Salts
Thiazoles
|
| IF |
1.863
|
| 引用数 |
31
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
| リソース情報 |
| ヒト・動物細胞 |
|
