Albanol A from the root bark of Morus alba L. induces apoptotic cell death in HL60 human leukemia cell line
| Autor: | Takashi Suzuki, Toshihiro Akihisa, Hisashi Nagai, Keiichi Tabata, Hidekuni Fukushi, Masatoshi Nihei, Takashi Kikuchi |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Programmed cell death
HL60 Apoptosis Plant Roots chemistry.chemical_compound Cell Line Tumor Drug Discovery medicine Cytotoxic T cell Humans Topoisomerase II Inhibitors Receptor Benzofurans Leukemia Chemistry Terpenes General Chemistry General Medicine medicine.disease Molecular biology Antineoplastic Agents Phytogenic DNA Topoisomerases Type II Biochemistry DNA Topoisomerases Type I Cell culture Morus Topoisomerase-II Inhibitor Topoisomerase I Inhibitors |
| Zdroj: | Chemicalpharmaceutical bulletin. 58(4) |
| ISSN: | 1347-5223 |
| Popis: | Albanol A (1), isolated from the root bark extract of Morus alba (mulberry), was evaluated for the cytotoxic and apoptosis-inducing activities in human leukemia (HL60) cells, and for the inhibitory activity in human DNA topoisomerases (Topo) I and II. This compound showed potent cytotoxic activity (IC(50) 1.7 microM) on the cells, and potent inhibitory activity on topoisomerase II (IC(50) 22.8 microM). In addition, albanol A induced early apoptosis which was detected by observing the membrane phospholipid exposure in flow cytometry. Western blot analysis showed that albanol A markedly reduced the levels of procaspases-3, 8, and 9, while being increased the levels of cleaved caspases-3, 8, and 9. The Bax/Bcl-2 ratio was significantly increased by albanol A treatment. Furthermore, albanol A induced caspase-2 activation. These results suggested that albanol A induces apoptotic cell death in HL60 via both the cell death receptor pathway by stimulation of death receptor, and the mitochondrial pathway by Topo II inhibition through caspase-2 activation. Therefore, albanol A may be a promising lead compound for developing an effective drug for treatment of leukemia. |
| Databáze: | OpenAIRE |
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