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dc.contributor.authorKikuchi T.en_US
dc.contributor.authorAkazawa H.en_US
dc.contributor.authorTabata K.en_US
dc.contributor.authorManosroi A.en_US
dc.contributor.authorManosroi J.en_US
dc.contributor.authorSuzuki T.en_US
dc.contributor.authorAkihisa T.en_US
dc.description.abstractEleven triterpene acids, 1-11, isolated from the leaves of Eriobotrya japonica, were evaluated for inhibition of DNA topoisomerase (Topo) I and cytotoxicity against human leukemia (HL60) and melanoma cell lines (CRL1579). Among the compounds tested, four compounds, d-oleanolic acid (4), ursolic acid (5), 3-O-(E)-p-coumaroyl tormentic acid (8), and betulinic acid (10), exhibited potent Topo I inhibitory activity (IC50 20.3-36.5 μM) and cytotoxicity against HL60 (EC50 5.0-8.1 μM). Upon assessing the apoptosis-inducing activity in. HL60 cells, compound 8 exhibited induction of apoptosis detected by the observation of DNA fragmentation and membrane phospholipid exposure in flow cytometry. Western blot analysis showed that compound 8 markedly reduced the levels of procaspases-3 and 9, while being increased the levels of cleaved caspases-3 and 9. On the other hand, compound 8 exerted almost no influence on the expression of caspase-8. In addition, compound 8 increased significantly Bax/Bcl-2 ratio and activated caspase-2. These results suggested that compound 8 induced apoptotic cell death in HL60 via mainly mitochondrial pathway by, at least in part, Topo I inhibition. Therefore, compound 8 may be promising lead compound for developing an effective drug for treatment of leukemia. © 2011 Pharmaceutical Society of Japan.en_US
dc.title3-O-(E)-p-coumaroyl tormentic acid from Eriobotrya japonica leaves induces caspase-dependent apoptotic cell death in human leukemia cell lineen_US
article.title.sourcetitleChemical and Pharmaceutical Bulletinen_US
article.hindex53en_US of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan; School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan; Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailanden_US, T.; College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan; email:
Appears in Collections:PHARMACY: Journal Articles

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