Albanol A from the Root Bark of Morus alba L. Induces Apoptotic Cell Death in HL60 Human Leukemia Cell Line

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概要

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• 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 (IC50 1.7 μM) on the cells, and potent inhibitory activity on topoisomerase II (IC50 22.8 μM). 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.

著者

• Tabata Keiichi

  日本大学 薬学部臨床医学ユニット

• Kikuchi Takashi

  College of Science and Technology, Nihon University

• Nihei Masatoshi

  College of Science and Technology, Nihon University

• Nagai Hisashi

  College of Science and Technology, Nihon University

• Fukushi Hidekuni

  College of Science and Technology, Nihon University

• Tabata Keiichi

  College of Pharmacy, Nihon University

• Suzuki Takashi

  College of Pharmacy, Nihon University

• Akihisa Toshihiro

  College of Science and Technology, Nihon University

• Akihisa Toshihiro

  College Of Science And Technology Nihon University

• Tabata Keiichi

  School Of Pharmacy Nihon University

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