TY - JOUR
T1 - Abietane diterpenes from Salvia miltiorrhiza inhibit the activation of hypoxia-inducible factor-1
AU - Nguyen, Tien Dat
AU - Jin, Xuejun
AU - Lee, Jeong Hyung
AU - Lee, Dongho
AU - Hong, Young Soo
AU - Lee, Kyeong
AU - Young, Ho Kim
AU - Jung, Joon Lee
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34548098412&partnerID=8YFLogxK
U2 - 10.1021/np060482d
DO - 10.1021/np060482d
M3 - Article
C2 - 17583950
AN - SCOPUS:34548098412
SN - 0163-3864
VL - 70
SP - 1093
EP - 1097
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 7
ER -