Albanol A from the root bark of Morus alba L. induces apoptotic cell death in HL60 human leukemia cell line.

Abstract

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.

• Authors: Takashi Kikuchi, Masatoshi Nihei, Hisashi Nagai, Hidekuni Fukushi, Keiichi Tabata, Takashi Suzuki, Toshihiro Akihisa
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 58 Issue 4 Pg. 568-71 (Apr 2010) ISSN: 1347-5223 [Electronic] Japan
• PMID: 20410645 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Benzofurans
• Terpenes
• Topoisomerase I Inhibitors
• Topoisomerase II Inhibitors
• mulberrofuran G
• DNA Topoisomerases, Type I
• DNA Topoisomerases, Type II

Topics

• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Benzofurans (isolation & purification, pharmacology)
• Cell Line, Tumor
• DNA Topoisomerases, Type I (metabolism)
• DNA Topoisomerases, Type II (metabolism)
• Humans
• Leukemia (drug therapy)
• Morus (chemistry)
• Plant Roots (chemistry)
• Terpenes (isolation & purification, pharmacology)
• Topoisomerase I Inhibitors
• Topoisomerase II Inhibitors