دورية أكاديمية
Dehydrocostuslactone suppresses angiogenesis in vitro and in vivo through inhibition of Akt/GSK-3β and mTOR signaling pathways.
| العنوان: | Dehydrocostuslactone suppresses angiogenesis in vitro and in vivo through inhibition of Akt/GSK-3β and mTOR signaling pathways. |
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| المؤلفون: | Chih-Ya Wang, An-Chi Tsai, Chieh-Yu Peng, Ya-Ling Chang, Kuo-Hsiung Lee, Che-Ming Teng, Shiow-Lin Pan |
| المصدر: | PLoS ONE, Vol 7, Iss 2, p e31195 (2012) |
| بيانات النشر: | Public Library of Science (PLoS), 2012. |
| سنة النشر: | 2012 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | The traditional Chinese medicine component dehydrocostuslactone (DHC) isolated from Saussurea costus (Falc.) Lipschitz, has been shown to have anti-cancer activity. Angiogenesis is an essential process in the growth and progression of cancer. In this study, we demonstrated, for the first time, the anti-angiogenic mechanism of action of DHC to be via the induction of cell cycle progression at the G0/G1 phase due to abrogation of the Akt/glycogen synthase kinase-3β (GSK-3β)/cyclin D1 and mTOR signaling pathway. First, we demonstrated that DHC has an anti-angiogenic effect in the matrigel-plug nude mice model and an inhibitory effect on human umbilical vein endothelial cell (HUVEC) proliferation and capillary-like tube formation in vitro. DHC caused G0/G1 cell cycle arrest, which was associated with the down-regulation of cyclin D1 expression, leading to the suppression of retinoblastoma protein phosphorylation and subsequent inhibition of cyclin A and cdk2 expression. With respect to the molecular mechanisms underlying the DHC-induced cyclin D1 down-regulation, this study demonstrated that DHC significantly inhibits Akt expression, resulting in the suppression of GSK-3β phosphorylation and mTOR expression. These effects are capable of regulating cyclin D1 degradation, but they were significantly reversed by constitutively active myristoylated (myr)-Akt. Furthermore, the abrogation of tube formation induced by DHC was also reversed by overexpression of Akt. And the co-treatment with LiCl and DHC significantly reversed the growth inhibition induced by DHC. Taken together, our study has identified Akt/GSK-3β and mTOR as important targets of DHC and has thus highlighted its potential application in angiogenesis-related diseases, such as cancer. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | http://europepmc.org/articles/PMC3281050?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0031195 |
| URL الوصول: | https://doaj.org/article/81fb43a7e7654288a2f202d5341bb626 |
| رقم الأكسشن: | edsdoj.81fb43a7e7654288a2f202d5341bb626 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0031195 |