کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8336980 1540649 2015 65 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
5-Demethylnobiletin promotes the formation of polymerized tubulin, leads to G2/M phase arrest and induces autophagy via JNK activation in human lung cancer cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
5-Demethylnobiletin promotes the formation of polymerized tubulin, leads to G2/M phase arrest and induces autophagy via JNK activation in human lung cancer cells
چکیده انگلیسی
5-Demethylnobiletin is a hydroxylated polymethoxyflavone found in citrus plants that shows antiproliferative activities in several cancer cell lines. In this study, we investigated the effects and underlying molecular mechanisms of 5-demethylnobiletin on inhibition of cell growth, apoptosis, cell cycle and autophagy in A549 and CL1-5 lung cancer cells. The results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay suggested that 5-demethylnobiletin inhibited cell growth in a dose- and time-dependent manner. Flow cytometry results suggested that 5-demethylnobiletin inhibited proliferation in lung cancer cells by inducing G2/M cell cycle phase arrest but predominantly not through apoptosis. Western blot results illustrated that the blockade of the cell cycle was associated with reduced levels of cdc25 and cdc2. Notably, our results indicated that 5-demethylnobiletin induced significant abnormal microtubule dynamics in A549 and CL1-5 cells, a novel finding. Studies conducted with isolated tubulin and docking models suggest that 5-demethylnobiletin promoted the polymerization of microtubules and bound to the taxol site. Additionally, 5-demethylnobiletin might also induce autophagy via activation of the JNK signaling pathway in A549 and CL1-5 cells. Pretreatment of the cells with the autophagy inhibitor 3-methyladenine significantly potentiated 5-demethylnobiletin-induced apoptosis, suggesting that 5-demethylnobiletin-induced autophagy mitigated cell apoptosis. Further investigation revealed that 5-demethylnobiletin inhibition of CL1-5 lung cancer cell growth was reproducible in a nude mouse model. Taken together, these studies suggest that 5-demethylnobiletin has anti-lung cancer efficacy both in vitro and in vivo possibly through induction of G2/M arrest, autophagy and apoptosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Nutritional Biochemistry - Volume 26, Issue 5, May 2015, Pages 484-504
نویسندگان
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