title: Thyrsiferol Inhibits Mitochondrial Respiration and HIF-1 Activation.
abstract: The cytotoxic marine red algal metabolite thyrsiferol (1) was found to inhibit hypoxia-induced hypoxia-inducible factor-1 (HIF-1) activation in T47D human breast tumor cells (66% inhibition at 3 μM). Compound 1 also suppressed hypoxic induction of HIF-1 target genes (VEGF, GLUT-1) at the mRNA level, and displayed tumor cell line-selective time-dependent inhibition of cell viability/proliferation. Mechanistic studies revealed that 1 selectively suppressed mitochondrial respiration at Complex I (IC(50) 3 μM). Thyrsiferol represents a prototypical, structurally unique electron transport chain inhibitor. The apparent rotenone-like activity may contribute to the observed cytotoxicity of 1 and play an important role in Laurencia chemical defense.
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS 38677, United States.
authors.forename: Fakhri
authors.initials: F
authors.lastname: Mahdi
authors.forename: Miriam
authors.initials: M
authors.lastname: Falkenberg
authors.forename: Efstathia
authors.initials: E
authors.lastname: Ioannou
authors.forename: Vassilios
authors.initials: V
authors.lastname: Roussis
authors.forename: Yu-Dong
authors.initials: YD
authors.lastname: Zhou
authors.forename: Dale G
authors.initials: DG
authors.lastname: Nagle