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KMID : 0545120090190080787
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Journal of Microbiology and Biotechnology
2009 Volume.19 No. 8 p.787 ~ p.791
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Heptelidic Acid, a Sesquiterpene Lactone, Inhibits Etoposide-Induced Apoptosis in Human Leukemia U937 Cells
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Kim Jin-Hee
Lee Choong-Hwan
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Abstract
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In the course of screening for substances that inhibit etoposide (10 ￥ig/ml)-induced apoptosis in human leukemia U937 cells, fungal strain F000120, which exhibits potent inhibitory activity, was selected. The active compound was purified from an ethyl acetate extract of the microorganism by Sep-pak C18 column chromatography and HPLC, and was identified as heptelidic acid (koningic acid) by spectroscopic methods. This compound inhibited caspase- 3 induction in U937 cells with an IC50 value of 40 ￥iM after 8 h of etoposide treatment. Fluorescent dye staining with acridine orange and ethidium bromide showed that heptelidic acid inhibited apoptosis. Furthermore, it was found that DNA fragmentation and caspase-3 activation, the biological hallmarks of apoptosis, were inhibited by the compound in a dose-dependent manner, suggesting that heptelidic acid inhibits etoposide-induced apoptosis via downregulation of caspases.
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KEYWORD
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Apoptosis, heptelidic acid, U937 cells
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