β-D-Xylopyranosyl-(1→3)-β-D-glucuronopyranosyl Echinocystic Acid Isolated from the Roots of Codonopsis lanceolata Induces Caspase-Dependent Apoptosis in Human Acute Promyelocytic Leukemia HL-60 Cells(Pharmacognosy)
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概要
- 論文の詳細を見る
We previously demonstrated that β-D-xylopyranosyl-(1→3)-β-D-glucuronopyranosyl echinocystic acid (codonoposide 1c), a biologically active compound isolated from the roots of Codonopsis lanceolata, is cytotoxic to cancer cells. In the present study, we investigated the effects of codonoposide 1c on the induction of apoptosis, and its putative action pathway in HL-60 human promyelocytic leukemia cells. Codonoposide 1c-treated HL-60 cells displayed several features of apoptosis, including DNA fragmentation, formation of DNA ladders by agarose gel electrophoresis, and externalization of annexin-V targeted phosphatidylserine (PS) residues. We observed that codonoposide 1c caused activation of caspase-8, caspase-9, and caspase-3. A broad caspase inhibitor (z-VAD-fmk), caspase-8 inhibitor (z-IETD-fmk), and caspase-3 inhibitor (z-DEVD-fmk) almost completely suppressed codonoposide 1c-induced DNA fragmentation. We further found that codonoposide 1c induces mitochondrial translocation of Bid from cytosol, reduction of cytosolic Bax, and cytochrome c release from mitochondria. Interestingly, codonoposide 1c also triggered the mitochondrial release of Smac/DIABLO (second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with a low isoelectric point) into cytosol, and a reduction in X-linked inhibitor of apoptosis protein (XIAP). Taken together, our data indicate that codonoposide 1c is a potent inducer of apoptosis and facilates its activity via Bid cleavage and translocation to mitochondria, Bax reduction in cytosol, release of cytochrome c and Smac/DIABLO into the cytosol, and subsequently caspase activation, providing a potential mechanism for the cytotoxic activity of codonoposide 1c.
- 社団法人日本薬学会の論文
- 2005-05-01
著者
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Lee Kyung-tae
韓国
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Lee Kyung-tae
College Of Pharmacy Kyung-hee University
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Lee Kyung-tae
Coll. Of Pharmacy Kyung-hee Univerisity
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Lee Kyung-tae
Department Of Life And Nanopharmaceutical Sciences College Of Pharmacy Kyung Hee University
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Lee Kyung-tae
Coll. Of Medical Sci. Kyung Hee Univ.
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Lee Kyung
College Of Pharmacy Dongdaemun-ku Hoegi-dong Kyung-hee University
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Lee Kyung-tae
Department Of Biochemistry College Of Pharmacy Kyung Hee University
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Park Hee-juhn
Department Of Pharmaceutical Engineering Sangji University
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Park Hee-juhn
韓国
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Park Hee-juhn
Division Of Applied Plant Sciences Sangji University
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Park Hee-juhn
Department Of Botanical Resources Sangi University
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Kim Deog
College Of Pharmacy Kyung Hee University
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JUNG Hyun
Division of Applied Plant Sciences, Sangji University
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PARK Hee
Division of Applied Plant Sciences, Sangji University
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LEE Jin
College of Oriental Medicine, Kyung Hee University
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JUNG Hyun-Ju
Division of Applied Plant Sciences, Sangji University
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Jeong H‐j
Dep. Of Oriental Pharmacy Wonkwang Univ.
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Lee Kyung
College Of Pharmacy Kyung Hee University
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Lee Kyung-won
韓国
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Lee Kyung‐won
Kyung Hee Univ. Seoul Kor
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Lee J‐y
Department Of Food And Nutrition Pusan National University
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Jung Hyuk-sang
Department Of Anatomy College Of Oriental Medicine Kyung Hee University
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Park Hee-joun
Department Of Botanical Resources Sangji University
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Kim Dong-hyun
Department Of Life And Nanopharmaceutical Sciences And Department Of Pharmaceutical Science Kyung He
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Kim Deog
College Of Oriental Medicine Kyung Hee University
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Lee J‐y
Kyung Hee Univ. Seoul Kor
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Jung Hyun-ju
Coll. Of Pharmacy And Wonkwang-oriental Medicines Res. Inst. Wonkwang Univ.
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Lee Kyung-Won
College of Pharmacy Kyung Hee University
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Lee Kyung
College of Medicine, Konyang University
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