Thyrsiferol Inhibits Mitochondrial Respiration and HIF-1 Activation |
| |
Authors: | Mahdi Fakhri Falkenberg Miriam Ioannou Efstathia Roussis Vassilios Zhou Yu-Dong Nagle Dale G |
| |
Institution: | Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS 38677, United States. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|