title: Isolation of apoptosis- and differentiation-inducing substances toward human promyelocytic leukemia HL-60 cells from leaves of Juniperus taxifolia.
abstract: A chloroform extract of the leaves of Juniperas taxifolia exhibited a marked antiproliferative effect on human promyelocytic leukemia HL-60 cells at a concentration of 2.5 microg/ml. Deoxypodophyllotoxin (4) was identified in the extract as an outstanding antiproliferative compound, and five diterpenes (1-3, 5, and 6) were isolated as known compounds with weak or no cytotoxicity. These compounds were examined for their respective apoptosis- and differentiation-inducing activities toward HL-60 cells by DNA fragmentation and NBT-reducing assays, respectively. Among them, 7alpha-hydroxysandaracopimaric acid (6) was found to have a potent differentiation-inducing activity in a dose-dependent manner at 0.125-2 microg/ml (0.39-6.29 microM), together with apoptosis-inducing activity at concentrations of more than 2.5 microg/ml (7.86 microM). Deoxypodophyllotoxin (4) that exerted cytotoxic and apoptosis-inducing activities at 2 ng/ml (5 nM) did not induce differentiation at the same concentration, and the other diterpenes (1-3 and 5) showed no effect on cell differentiation, even at 5 microg/ml. It was thus demonstrated for the first time that 7alpha-hydroxysandaracopimaric acid was an effective differentiation-inducing compound toward HL-60 cells.
authors.affiliation: Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara 727-0023, Japan. muto@pu-hiroshima.ac.jp
authors.forename: Norio
authors.initials: N
authors.lastname: Muto
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Tomokuni
authors.forename: Mari
authors.initials: M
authors.lastname: Haramoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Tatemoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Inatomi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Murata
authors.forename: Akira
authors.initials: A
authors.lastname: Inada
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D018653:Juniperus / Q000737:chemistry*; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D009682:Magnetic Resonance Spectroscopy; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D010936:Plant Extracts