RRC ID |
44233
|
著者 |
Kikuchi T, Pan X, Ishii K, Nakamura Y, Ogihara E, Koike K, Tanaka R, Akihisa T.
|
タイトル |
Cytotoxic and apoptosis-inducing activities of 12-O-Acetylazedarachin B from the fruits of Melia azedarach in human cancer cell lines.
|
ジャーナル |
Biol Pharm Bull
|
Abstract |
12-O-Acetylazedarachin B (1), isolated from the fruit extract of Melia azedarach, exhibited potent cytotoxicity against leukemia (HL-60) (IC(50) 0.016 µM) and stomach (AZ521) (IC(50) 0.035 µM) cancer cell lines. Upon assessing the apoptosis-inducing activity in HL-60 cells, compound 1 exhibited induction of apoptosis detected by the observation of membrane phospholipid exposure and DNA fragmentation in flow cytometry. Western blot analysis showed that 1 markedly reduced the levels of procaspases-3, 8, and 9, while being increased the levels of cleaved caspases-3, 8, and 9. In addition, compound 1 increased significantly Bax/Bcl-2 ratio. These results suggested that 1 induced apoptotic cell death in HL-60 via both mitochondrial and death receptor-mediated pathways. Therefore, compound 1 may be promising lead compound for developing an effective drug for treatment of leukemia. Flow cytometric analysis suggested that the cytotoxicity of 1 against AZ521 is due to inducing apoptosis as well as necrosis with the latter predominated.
|
巻・号 |
36(1)
|
ページ |
135-9
|
公開日 |
2013-1-1
|
DOI |
10.1248/bpb.b12-00795
|
PII |
DN/JST.JSTAGE/bpb/b12-00795
|
PMID |
23302647
|
MeSH |
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Cycle / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Fruit
Humans
Limonins / isolation & purification
Limonins / pharmacology*
Melia azedarach*
Plant Extracts / pharmacology
|
IF |
1.863
|
引用数 |
16
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
リソース情報 |
ヒト・動物細胞 |
HL60(RCB0041)
A549(RCB0098)
SK-BR-3 |