4-Hydroxyderricin from Angelica keiskei Roots Induces Caspase-dependent Apoptotic Cell Death in HL60 Human Leukemia Cells
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- Akihisa Toshihiro
- College of Science and Technology, Nihon University
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- Kikuchi Takashi
- College of Science and Technology, Nihon University
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- Nagai Hisashi
- College of Science and Technology, Nihon University
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- Ishii Koichi
- College of Science and Technology, Nihon University
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- Tabata Keiichi
- School of Pharmacy, Nihon University
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- Suzuki Takashi
- School of Pharmacy, Nihon University
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The ethyl acetate (EtOAc)-soluble fraction of a methanol extract of Angelica keiskei roots exhibited cytotoxic activity against 4 human tumor cell lines, HL60 (leukemia), CRL1579 (melanoma), A549 (lung), and AZ521 (stomach). Nine chalcones (1–9), 5 coumarins (10–14), and 4 flavanones (15–18), isolated from the EtOAc-soluble fraction, were examined for their cytotoxic activities in the 4 human tumor cell lines. Among the compounds tested, 4-hydroxyderricin (2), a major chalcone constituent, exhibited potent cytotoxic activities in all 4 tumor cell lines with IC50 values of 5.5 μM (HL60), 4.8 μM (CRL1579), 10.2 μM (A549), and 4.2 μM (AZ521). 4-Hydroxyderricin induced early apoptosis in HL60 cells, observed as membrane phospholipid exposure in flow cytometry. Western blot analysis showed that 4-hydroxyderricin markedly reduced the levels of procaspases-3, -8, and -9, while increasing the levels of cleaved caspases-3, -8, and -9. In addition, 4-hydroxyderricin exhibited potent inhibitory activity on human DNA topoisomerase (Topo) II (IC50 21.9 μM). These results suggested that 4-hydroxyderricin induces apoptotic cell death in HL60 via both the death receptor-mediated pathway and the mitochondrial pathway by, at least in part, Topo II inhibition. 4-Hydroxyderricin may therefore hold promise as an effective antitumor agent.
収録刊行物
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- Journal of Oleo Science
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Journal of Oleo Science 60 (2), 71-77, 2011
公益社団法人 日本油化学会
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詳細情報 詳細情報について
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- CRID
- 1390282679069109632
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- NII論文ID
- 130000438329
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- NII書誌ID
- AA11503337
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- COI
- 1:STN:280:DC%2BC3M7ktVKrug%3D%3D
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- ISSN
- 13473352
- 13458957
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- NDL書誌ID
- 10942746
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- PubMed
- 21263202
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可