Oncotarget

Research Papers:

Tanshinone I inhibits tumor angiogenesis by reducing STAT3 phosphorylation at TYR705 and hypoxia-induced HIF-1α accumulation in both endothelial and tumor cells

Yan Wang _, Jia-Xin Li, Ying-Qing Wang and Ze-Hong Miao

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Oncotarget. 2015; 6:16031-16042. https://doi.org/10.18632/oncotarget.3648

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Abstract

Yan Wang1,2, Jia-Xin Li1, Ying-Qing Wang1, Ze-Hong Miao1

1Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

2College of Pharmacy, Nanchang University, Nanchang 330006, China

Correspondence to:

Ze-Hong Miao, e-mail: zhmiao@simm.ac.cn

Ying-Qing Wang, e-mail: yqwang@simm.ac.cn

Keywords: tanshinone I, angiogenesis, Stat3, HIF-1α, VEGF

Received: February 15, 2015     Accepted: March 23, 2015     Published: April 10, 2015

ABSTRACT

Tanshinone I (Tanshinone-1), a major active principle of Salvia miltiorrhiza (Danshen), has been shown to overcome tumor drug resistance and metastasis. Here we report that tanshinone-1 inhibits angiogenesis. Tanshinone-1 inhibited proliferation, migration and tube formation of vascular endothelial cells, rat aortic ring sprouting and the neovascularization of the chick chorioallantoic membrane in a concentration-dependent manner. In endothelial cells, tanshinone-1 almost completely inhibited phosphorylation of Stat3 at Tyr705 regardless of hypoxia or normoxia but only slightly decreased the hypoxia-induced HIF-1α accumulation. In tumor cells, contrastively, tanshinone-1 could not only make phosphorylation of Stat3 at Tyr705 disappear but also reduce the hypoxia-induced accumulation of HIF-1α to its baseline levels at normoxia. Consequently, VEGF secretion from tumor cells was reduced, which could potentiate the direct inhibition of tanshinone-1 on endothelial cells. Together with its overcoming tumor drug resistance and metastasis, our results reveal unique characteristics of tanshinone-1 and its improved derivatives as promising angiogenesis inhibitors.


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