Terpenoid Tetrahydroisoquinoline Alkaloids Emetine, Klugine, and Isocephaeline Inhibit the Activation of Hypoxia-Inducible Factor-1 in Breast Tumor Cells

Klugine (1), isocephaeline (2), and emetine (4) inhibited hypoxia-inducible factor-1 (HIF-1) activation by hypoxia in T47D breast tumor cells (IC(50) values 0.2, 1.1, and 0.11 muM, respectively). Compounds 1, 2, and 4 inhibited both hypoxia- and iron chelator-induced HIF-1 activation by blocking HIF-1alpha protein accumulation.