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KMID : 1140120080130040262
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Cancer Prevention Research
2008 Volume.13 No. 4 p.262 ~ p.270
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Park Cheol
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Abstract
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Esculetin, a coumarin derivative contained in various plants such as Artemisia scoparia, A. capillaries, Ceratostigma willmottianum and in the leaves of Citrus limonia, has been shown to exhibit antioxidant, anti-inflammatory and anti-cancer effects. However, the cellular and molecular mechanism of its action are poorly understood. The aim of the present study was to further elucidate the possible mechanisms by which esculetin exerts its anti-proliferative action and apoptosis in human cancer cells. It was found that the growth inhibitory effects of esculetin were more sensitive in human leukemic cell lines (U937, HL-60 and K562) than in human solid cancer cell lines such as lung cancer (NCI-H460 and A549), breast cancer (MCF-7 and MDA-MB-231), colon cancer (HCT116 and HT29) and hepatocarcinoma (HepG2 and Hep3B) cells. The anti-proliferative effect of esculetin treatment in human leukemic U937 cells was associated apoptosis as determined by the loss of mitochondrial membrane potential (MMP, Δψm), formation of chromatin condensation, and a flow cytometry analysis. However, an extracellular signal-regulated kinase (ERK)-specific inhibitor, PD98059, and a c-Jun N-terminal kinase (JNK)-specific inhibitor, SP600125, significantly blocked esculetin-induced apoptosis in U937 cells by inhibiting the increases sub-G1 population, formation of chromatin condensation, loss of MMP, induction of DR4, and degradation of β-catenin and DEE45/ICAD. These results indicated that the JNK and ERK pathways were key regulators of apoptosis in response to esculetin in human leukemia U937 cells.
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KEYWORD
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Esculetin, Apoptosis, U937, ERK, JNK
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