Abietane diterpenes from Salvia miltiorrhiza inhibit the activation of hypoxia-inducible factor-1

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Title
Abietane diterpenes from Salvia miltiorrhiza inhibit the activation of hypoxia-inducible factor-1
Author(s)
N T Dat; X Jin; J H Lee; D Lee; Young-Soo Hong; Kyeong Lee; Y H Kim; Jung Joon Lee
Bibliographic Citation
Journal of Natural Products, vol. 70, no. 7, pp. 1093-1097
Publication Year
2007
Abstract
The hypoxia-inducible factor-1 (HIF-1) has been known to be correlated to the adaptation and proliferation of tumor cells; therefore HIF-1 has become an important target in the development of anticancer drugs. A phytochemical study of the CHCl3-soluble fraction of Salvia miltiorrhiza, which strongly inhibited hypoxia-induced reporter gene expression, led to the isolation of 12 abietane-type diterpenes. of these compounds, sibiriquinone A (1), sibiriquinone B (2), cryptotanshinone (3), and dihydrotanshinone I (4) potently inhibited hypoxia-induced luciferase expression with IC50 values of 0.34, 3.36, 1.58, and 2.05 μM on AGS cells, a human gastric cancer cell line, and 0.28, 3.18, 1.36, and 2.29 μM on Hep3B cells, a human hepatocarcinoma cell line, respectively. Consistently, 1 and 4 dose-dependently suppressed the HIF-1α accumulation and 1 inhibited mRNA expression of vascular endothelial growth factor (VEGF) under hypoxia. These results suggest that the anticancer activity of tanshinones is likely at least in part associated with their inhibition of HIF-1 accumulation.
ISSN
0163-3864
Publisher
Amer Chem Soc
DOI
http://dx.doi.org/10.1021/np060482d
Type
Article
Appears in Collections:
Ochang Branch Institute > Anticancer Agent Research Center > 1. Journal Articles
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