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标题：Cytotoxic and Apoptosis-Inducing Activities of 12-O-Acetylazedarachin B from the Fruits of Melia azedarach in Human Cancer Cell Lines
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作者：Takashi Kikuchi ; Xin Pan ; Koichi Ishii 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2013
卷号：36
期号：1
页码：135-139
DOI：10.1248/bpb.b12-00795
出版社：The Pharmaceutical Society of Japan
摘要：12- O -Acetylazedarachin B ( 1 ), isolated from the fruit extract of Melia azedarach , exhibited potent cytotoxicity against leukemia (HL-60) (IC₅₀ 0.016 µM) and stomach (AZ521) (IC₅₀ 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.
关键词：12-O-acetylazedarachin B;Melia azedarach;cytotoxic activity;apoptosis;limonoid