title: 2-O-methylisohemigossylic acid lactone, a sesquiterpene, isolated from roots of mokumen (Gossampinus malabarica) induces cell death and morphological change indicative of apoptotic chromatin condensation in human promyelotic leukemia HL-60 cells.
abstract: 2-O-methylisohemigossylic acid lactone, a sesquiterpene, was purified from roots of mokumen (Gossampinus malabarica) and identified by Mass, and (1)H- and (13)-NMR. This sesquiterpene displayed strong growth inhibitory effect against human promyelotic leukemia HL-60 cells. Apoptotic morphological change of the nucleus, including chromatin condensation was induced in the HL-60 cells treated with the sesquiterpene. The fragmentation of DNA by the sesquiterpene to oligonucleosomal-sized fragments, a characteristic of apoptosis, was observed to be dose- and time-dependent in the HL-60 cells. Inhibitors of caspases suppressed the DNA fragmentation induced by the sesquiterpene. These findings suggest that growth inhibition by the sesquiterpene of HL-60 cells results from the induction of apoptosis by the sesqui-terpene, and that caspase cascade is involved in the induction of apoptosis by the compound in the HL-60 cells.
authors.affiliation: Faculty of Medicine, Mie University, Mie 514-0001, Japan.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Hibasami
authors.forename: Kazumi
authors.initials: K
authors.lastname: Saitoh
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Katsuzaki
authors.forename: Kunio
authors.initials: K
authors.lastname: Imai
authors.forename: Yue
authors.initials: Y
authors.lastname: Aratanechemuge
authors.forename: Takashi
authors.initials: T
authors.lastname: Komiya
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D035161:Bombacaceae / Q000737:chemistry*; D020169:Caspases / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002843:Chromatin / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology*; D008214:Lymphocytes / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D018517:Plant Roots / Q000737:chemistry*; D012717:Sesquiterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: C499969:2-O-methylisohemigossylic acid lactone; D000975:Antioxidants; D002843:Chromatin; D004791:Enzyme Inhibitors; D012717:Sesquiterpenes; D020169:Caspases