Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Cytotoxic and Apoptosis-Inducing Activities of 12-O-Acetylazedarachin B from the Fruits of Melia azedarach in Human Cancer Cell Lines
Takashi KikuchiXin PanKoichi IshiiYasuhiro NakamuraEri OgiharaKazuo KoikeReiko TanakaToshihiro Akihisa
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2013 年 36 巻 1 号 p. 135-139

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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.

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© 2013 The Pharmaceutical Society of Japan
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