Abietane diterpenes from Salvia miltiorrhiza inhibit the activation of hypoxia-inducible factor-1.
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 microM on AGS cells, a human gastric cancer cell line, and 0.28, 3.18, 1.36, and 2.29 microM on Hep3B cells, a human hepatocarcinoma cell line, respectively. Consistently, 1 and 4 dose-dependently suppressed the HIF-1alpha 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.
Dat
Nguyen Tien
NT
Molecular Cancer Research Center, Korean Research Institute of Biosciences and Biotechnology, Daejeon 305-333, Korea.
Jin
Xuejun
X
Lee
Jeong-Hyung
JH
Lee
Dongho
D
Hong
Young-Soo
YS
Lee
Kyeong
K
Kim
Young Ho
YH
Lee
Jung Joon
JJ
D045784:Abietanes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors*; D007723:Korea; D010946:Plants, Medicinal / Q000737:chemistry*; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D051793:Hypoxia-Inducible Factor 1