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Depression: 21st Century Solutions + The Dark Side of Wheat

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Article Publish Status: FREE
Abstract Title:

Tanshinone IIA inhibits HIF-1α and VEGF expression in breast cancer cells via mTOR/p70S6K/RPS6/4E-BP1 signaling pathway.

Abstract Source:

PLoS One. 2015 ;10(2):e0117440. Epub 2015 Feb 6. PMID: 25659153

Abstract Author(s):

Guobing Li, Changyu Shan, Lei Liu, Ting Zhou, Jing Zhou, Xiaoye Hu, Yibiao Chen, Hongjuan Cui, Ning Gao

Article Affiliation:

Guobing Li

Abstract:

Hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) play important roles in angiogenesis and tumor growth. Tanshinone IIA (T2A) is a novel antiangiogenic agent with promising antitumor effects; however, the molecular mechanism underlying the antiangiogenic effects of T2A remains unclear. In the present study, we provided evidence showing that T2A inhibited angiogenesis and breast cancer growth by down-regulating VEGF expression. Specifically, T2A repressed HIF-1α expression at the translational level and inhibited the transcriptional activity of HIF-1α, which led to the down-regulation of VEGF expression. Suppression of HIF-1α synthesis by T2A correlated with strong dephosphorylation of mammalian target of rapamycin (mTOR) and its effectors ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), a pathway regulating HIF-1α expression at the translational level. In addition, we also found that T2A inhibited the angiogenesis and growth of human breast cancer xenografts in nude mice through suppression of HIF-1α and VEGF. Our study provides novel perspectives and potential targets for the treatment of human breast cancer.

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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