دورية أكاديمية
Degradation of Mcl-1 through GSK-3β Activation Regulates Apoptosis Induced by Bufalin in Non-Small Cell Lung Cancer H1975 Cells
| العنوان: | Degradation of Mcl-1 through GSK-3β Activation Regulates Apoptosis Induced by Bufalin in Non-Small Cell Lung Cancer H1975 Cells |
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| المؤلفون: | Xiao-hong Kang, Jing-hang Zhang, Qing-qin Zhang, Yan-hui Cui, Ying Wang, Wei-zheng Kou, Zhan-hui Miao, Ping Lu, Li-Fang Wang, Zhen-ye Xu, Fei Cao |
| المصدر: | Cellular Physiology and Biochemistry, Vol 41, Iss 5, Pp 2067-2076 (2017) |
| بيانات النشر: | Cell Physiol Biochem Press GmbH & Co KG, 2017. |
| سنة النشر: | 2017 |
| المجموعة: | LCC:Physiology LCC:Biochemistry |
| مصطلحات موضوعية: | NSCLC, Bufalin, Mcl-1, Glycogen synthase kinase-3β, Apoptosis, Physiology, QP1-981, Biochemistry, QD415-436 |
| الوصف: | Background/Aims: Mcl-1, an anti-apoptotic Bcl-2 family member, is often overexpressed in non-small cell lung cancer (NSCLC). Bufalin has been reported to induce apoptosis in various tumor cells. However, there is no report showing that bufalin could downregulate Mcl-1 expression in NSCLC. Methods: Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay in H1975 cells. Cell apoptosis was detected by flow cytometry. Mcl-1 mRNA was detected by RT-PCR. The expression of apoptosis-associated proteins in H1975 cells was detected by western blotting. The levels of Mcl-1 ubiquitination and NOXA were analyzed by Immunoprecipitation assay. Results: Cell growth was inhibited by bufalin in a time and dose-dependent manner. Bufalin induced apoptosis in NSCLC cells by activating caspase cascades and downregulating Mcl-1 expression. However, overexpression of Mcl-1 diminished bufalin-induced apoptosis. Furthermore, bufalin did not reduce Mcl-1 mRNA expression in H1975 cells, but strongly promoted Mcl-1 protein degradation. Proteasome inhibitor MG132 markedly prevented the degradation of Mcl-1 and blocked bufalin-induced Mcl-1 reduction. Bufalin did not significantly affect NOXA protein levels, but downregulated the expression of p-GSK-3β. GSK-3 inhibitor and GSK-3β siRNA resulted in increased levels of Mcl-1 and reversed the bufalin-induced Mcl-1 degradation. Conclusion: Bufalin induced cell apoptosis in H1975 cells may be through downregulation of Mcl-1. Proteasomal degradation of Mcl-1 via GSK-3β activation was involved in bufalin-induced apoptosis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1015-8987 1421-9778 |
| Relation: | http://www.karger.com/Article/FullText/475438; https://doaj.org/toc/1015-8987; https://doaj.org/toc/1421-9778 |
| DOI: | 10.1159/000475438 |
| URL الوصول: | https://doaj.org/article/8bf7cc3200e24c1ba96562493589d31b |
| رقم الأكسشن: | edsdoj.8bf7cc3200e24c1ba96562493589d31b |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 10158987 14219778 |
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| DOI: | 10.1159/000475438 |