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) (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.
authors.affiliation: College of Science and Technology, Nihon University, 1–8–14 Kanda Surugadai, Chiyoda-ku, Tokyo 101–8308, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Xin
authors.initials: X
authors.lastname: Pan
authors.forename: Koichi
authors.initials: K
authors.lastname: Ishii
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Eri
authors.initials: E
authors.lastname: Ogihara
authors.forename: Kazuo
authors.initials: K
authors.lastname: Koike
authors.forename: Reiko
authors.initials: R
authors.lastname: Tanaka
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akihisa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005638:Fruit; D006801:Humans; D036701:Limonins / Q000302:isolation & purification / Q000494:pharmacology*; D031586:Melia azedarach; D010936:Plant Extracts / Q000494:pharmacology
chemical_list: C581896:12-O-acetylazedarachin B; D000970:Antineoplastic Agents; D036701:Limonins; D010936:Plant Extracts