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