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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概要

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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.

著者

• Tanaka Reiko

  Osaka University Of Pharmaceutical Sciences

• Kikuchi Takashi

  College of Science and Technology, Nihon University

• Ishii Koichi

  College of Science and Technology, Nihon University

• Akihisa Toshihiro

  College Of Science And Technology Nihon University

• KOIKE KAZUO

  School of Pharmaceutical Science, Toho University

• Pan Xin

  College of Science and Technology, Nihon University

• Nakamura Yasuhiro

  College of Science and Technology, Nihon University

• Ogihara Eri

  College of Science and Technology, Nihon University

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