کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2570541 | 1128590 | 2008 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Induction of apoptosis by esculetin in human leukemia U937 cells through activation of JNK and ERK
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موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
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چکیده انگلیسی
Esculetin is a phenolic compound that is found in various natural plant products and induces apoptosis in several types of human cancer cells. However, the underlying mechanisms of its action are not completely understood. In the present study, we used human leukemia cells to gain further insight into the mechanism of esculetin-induced anti-proliferative action and apoptosis. It was found that esculetin inhibits cell viability by inducing apoptosis, as evidenced by the formation of apoptotic bodies, DNA fragmentation, and the accumulation of cells in the sub-G1 phase. Esculetin-induced apoptosis was correlated with mitochondrial dysfunction, leading to the release of cytochrome c from the mitochondria to the cytosol, as well as the proteolytic activation of caspases. The z-DEVD-fmk caspase-3 inhibitor and the ectopic expression of anti-apoptotic Bcl-2 significantly inhibited esculetin-induced apoptosis, demonstrating the important role of caspase-3 and mitochondrial proteins in the observed cytotoxic effect. Furthermore, esculetin selectively increased the phosphorylation of extracellular-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not that of other kinases such as Akt and p38 activation. In addition, an ERK-specific inhibitor, PD98059, and a JNK-specific inhibitor, SP600125, showed inhibited sub-G1 phase DNA content, DNA fragmentation, caspase activation, and mitochondrial dysfunction induced by esculetin treatment. These results indicated that the JNK and ERK pathways were key regulators of apoptosis in response to esculetin in human leukemia U937 cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 227, Issue 2, 1 March 2008, Pages 219-228
Journal: Toxicology and Applied Pharmacology - Volume 227, Issue 2, 1 March 2008, Pages 219-228
نویسندگان
Cheol Park, Cheng-Yun Jin, Gi-Young Kim, Il-Whan Choi, Taeg Kyu Kwon, Byung Tae Choi, Su Jae Lee, Won Ho Lee, Yung Hyun Choi,