Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1α (HIF-1α) through inhibiting protein synthesis

✍ Scribed by Dae-Hee Lee; Yong J. Lee

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 285 KB
• Volume: 105
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21851

✦ Synopsis

Abstract

Quercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the proliferation of cancer cells and induce the accumulation of hypoxia‐inducible factor‐1α (HIF‐1α) in normoxia. In this study, under hypoxic conditions (1% O~2~), we examined the effect of quercetin on the intracellular level of HIF‐1α and extracellular level of vascular endothelial growth factor (VEGF) in a variety of human cancer cell lines. Surprisingly, we observed that quercetin suppressed the HIF‐1α accumulation during hypoxia in human prostate cancer LNCaP, colon cancer CX‐1, and breast cancer SkBr3 cells. Quercetin treatment also significantly reduced hypoxia‐induced secretion of VEGF. Suppression of HIF‐1α accumulation during treatment with quercetin in hypoxia was not prevented by treatment with 26S proteasome inhibitor MG132 or PI3K inhibitor LY294002. Interestingly, hypoxia (1% O~2~) in the presence of 100 µM quercetin inhibited protein synthesis by 94% during incubation for 8 h. Significant quercetin concentration‐dependent inhibition of protein synthesis and suppression of HIF‐1α accumulation were observed under hypoxic conditions. Treatment with 100 µM cycloheximide, a protein synthesis inhibitor, replicated the effect of quercetin by inhibiting HIF‐1α accumulation during hypoxia. These results suggest that suppression of HIF‐1α accumulation during treatment with quercetin under hypoxic conditions is due to inhibition of protein synthesis. J. Cell. Biochem. 105: 546–553, 2008. © 2008 Wiley‐Liss, Inc.