کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5828630 | 1558967 | 2013 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A novel anticancer agent Broussoflavonol B downregulates estrogen receptor (ER)-α36 expression and inhibits growth of ER-negative breast cancer MDA-MB-231 cells
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
Estrogen receptor (ER)-negative breast cancers are aggressive and unresponsive to antiestrogens, and current therapeutic modalities for ER-negative breast cancer patients are usually associated with strong toxicity and side effects. Less toxic and more effective targeted therapies are urgently needed to treat this type of breast cancer. Here, we report that Broussoflavonol B, a chemical purified from the bark of the Paper Mulberry tree (Broussonetia papyrifera) exhibited potent growth inhibitory activity in ER-negative breast cancer MDA-MB-231 cells at sub-micromolar concentrations. Broussoflavonol B induced cell cycle arrest at both the G0/G1 and G2/M phases accompanied by a downregulation of c-Myc protein, a upregulation of the cell cycle inhibitory proteins p16INK4a, p19INK4D and p21WAF1/CIP1 and a down-regulation of the expression levels of the G2/M regulatory proteins such as cyclin B1, cdc2 and cdc25C. Broussoflavonol B also induced apoptotic cell death characterized by accumulation of the annexin V- and propidium iodide-positive cells, and cleavage of caspases 8, 9 and 3. In addition, Broussoflavonol B treatment also decreased the steady state levels of the epidermal growth factor receptor (EGFR) and ER-α36, a variant of estrogen receptor-α, and restricted growth of the stem-like cells in ER-negative breast cancer MDA-MB-231 cells. Our results thus indicate that Broussoflavonol B is a potent growth inhibitor for ER-negative breast cancer cells and provide a rational for preclinical and clinical evaluation of Broussoflavonol B for ER-negative breast cancer therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 714, Issues 1â3, 15 August 2013, Pages 56-64
Journal: European Journal of Pharmacology - Volume 714, Issues 1â3, 15 August 2013, Pages 56-64
نویسندگان
MingXi Guo, MoLin Wang, Hao Deng, XinTian Zhang, Zhao-Yi Wang,