Reference - Detail
| RRC ID | 38609 |
|---|---|
| Author | Kikuchi T, Akazawa H, Tabata K, Manosroi A, Manosroi J, Suzuki T, Akihisa T. |
| Title | 3-O-(E)-p-coumaroyl tormentic acid from Eriobotrya japonica leaves induces caspase-dependent apoptotic cell death in human leukemia cell line. |
| Journal | Chem Pharm Bull (Tokyo) |
| Abstract |
Eleven 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, δ-oleanolic acid (4), ursolic acid (5), 3-O-(E)-p-coumaroyl tormentic acid (8), and betulinic acid (10), exhibited potent Topo I inhibitory activity (IC(50) 20.3-36.5 µM) and cytotoxicity against HL60 (EC(50) 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. |
| Volume | 59(3) |
| Pages | 378-81 |
| Published | 2011-1-1 |
| DOI | 10.1248/cpb.59.378 |
| PII | JST.JSTAGE/cpb/59.378 |
| PMID | 21372421 |
| MeSH | Antineoplastic Agents, Phytogenic / chemistry* Antineoplastic Agents, Phytogenic / isolation & purification Antineoplastic Agents, Phytogenic / toxicity Apoptosis* Caspase 2 / metabolism Caspase 3 / metabolism Caspase 8 / metabolism Caspase 9 / metabolism Caspases / metabolism Cell Line, Tumor Coumarins / chemistry* Coumarins / isolation & purification Coumarins / toxicity DNA Topoisomerases, Type I / chemistry* DNA Topoisomerases, Type I / metabolism Eriobotrya / chemistry* Humans Leukemia / drug therapy* Plant Leaves / chemistry Proto-Oncogene Proteins c-bcl-2 / metabolism Topoisomerase I Inhibitors / chemistry Topoisomerase I Inhibitors / isolation & purification Topoisomerase I Inhibitors / toxicity Triterpenes / chemistry* Triterpenes / isolation & purification Triterpenes / toxicity bcl-2-Associated X Protein / metabolism |
| IF | 1.416 |
| Times Cited | 15 |
| WOS Category | PHARMACOLOGY & PHARMACY CHEMISTRY, MULTIDISCIPLINARY CHEMISTRY, MEDICINAL |
| Resource | |
| Human and Animal Cells | |