Albanol A from the root bark of Morus alba L. induces apoptotic cell death in HL60 human leukemia cell line.
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.
Kikuchi
Takashi
T
College of Science and Technology, Nihon University, Tokyo, Japan.
Nihei
Masatoshi
M
Nagai
Hisashi
H
Fukushi
Hidekuni
H
Tabata
Keiichi
K
Suzuki
Takashi
T
Akihisa
Toshihiro
T
D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D031625:Morus / Q000737:chemistry*; D018517:Plant Roots / Q000737:chemistry; D013729:Terpenes / Q000302:isolation & purification / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D001572:Benzofurans; D013729:Terpenes; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C047825:mulberrofuran G; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II