Isolation of apoptosis- and differentiation-inducing substances toward human promyelocytic leukemia HL-60 cells from leaves of Juniperus taxifolia.
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.
Muto
Norio
N
Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara 727-0023, Japan. muto@pu-hiroshima.ac.jp
Tomokuni
Tatsuru
T
Haramoto
Mari
M
Tatemoto
Hideki
H
Nakanishi
Tsutomu
T
Inatomi
Yuka
Y
Murata
Hiroko
H
Inada
Akira
A
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
D010936:Plant Extracts