Cytotoxic and Apoptosis-Inducing Activities of 12-<i>O</i>-Acetylazedarachin B from the Fruits of <i>Melia azedarach</i> in Human Cancer Cell Lines

• Kikuchi Takashi

  College of Science and Technology, Nihon University Osaka University of Pharmaceutical Sciences

• Pan Xin

  College of Science and Technology, Nihon University

• Ishii Koichi

  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

• Koike Kazuo

  School of Pharmaceutical Sciences, Toho University

• Tanaka Reiko

  Osaka University of Pharmaceutical Sciences

• Akihisa Toshihiro

  College of Science and Technology, Nihon University

Bibliographic Information

Other Title

• Cytotoxic and Apoptosis-Inducing Activities of 12-O-Acetylazedarachin B from the Fruits of Melia azedarach in Human Cancer Cell Lines

Abstract

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.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 36 (1), 135-139, 2013

  The Pharmaceutical Society of Japan

Keywords

• 12-<i>O</i>-acetylazedarachin B
• <i>Melia azedarach</i>
• cytotoxic activity
• apoptosis
• limonoid

Details

• CRID: 1390001204633316096
• NII Article ID: 130003361355
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.b12-00795
• COI: 1:STN:280:DC%2BC3s3otFahuw%3D%3D
• ISSN: 13475215
• ISSN: 09186158
• NDL BIB ID: 024173651
• PubMed: 23302647
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I024173651
• Web Site: https://www.jstage.jst.go.jp/article/bpb/36/1/36_b12-00795/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2013228391
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed