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Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) through inhibiting protein synthesis.
J Cell Biochem. 2008 Oct 01; 105(2):546-53.JC

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-1alpha (HIF-1alpha) in normoxia. In this study, under hypoxic conditions (1% O(2)), we examined the effect of quercetin on the intracellular level of HIF-1alpha 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-1alpha 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-1alpha 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 microM quercetin inhibited protein synthesis by 94% during incubation for 8 h. Significant quercetin concentration-dependent inhibition of protein synthesis and suppression of HIF-1alpha accumulation were observed under hypoxic conditions. Treatment with 100 microM cycloheximide, a protein synthesis inhibitor, replicated the effect of quercetin by inhibiting HIF-1alpha accumulation during hypoxia. These results suggest that suppression of HIF-1alpha accumulation during treatment with quercetin under hypoxic conditions is due to inhibition of protein synthesis.

Authors+Show Affiliations

Department of Surgery and Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

18655183

Citation

Lee, Dae-Hee, and Yong J. Lee. "Quercetin Suppresses Hypoxia-induced Accumulation of Hypoxia-inducible Factor-1alpha (HIF-1alpha) Through Inhibiting Protein Synthesis." Journal of Cellular Biochemistry, vol. 105, no. 2, 2008, pp. 546-53.
Lee DH, Lee YJ. Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) through inhibiting protein synthesis. J Cell Biochem. 2008;105(2):546-53.
Lee, D. H., & Lee, Y. J. (2008). Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) through inhibiting protein synthesis. Journal of Cellular Biochemistry, 105(2), 546-53. https://doi.org/10.1002/jcb.21851
Lee DH, Lee YJ. Quercetin Suppresses Hypoxia-induced Accumulation of Hypoxia-inducible Factor-1alpha (HIF-1alpha) Through Inhibiting Protein Synthesis. J Cell Biochem. 2008 Oct 1;105(2):546-53. PubMed PMID: 18655183.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) through inhibiting protein synthesis. AU - Lee,Dae-Hee, AU - Lee,Yong J, PY - 2008/7/26/pubmed PY - 2009/1/6/medline PY - 2008/7/26/entrez SP - 546 EP - 53 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 105 IS - 2 N2 - Quercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the proliferation of cancer cells and induce the accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) in normoxia. In this study, under hypoxic conditions (1% O(2)), we examined the effect of quercetin on the intracellular level of HIF-1alpha 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-1alpha 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-1alpha 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 microM quercetin inhibited protein synthesis by 94% during incubation for 8 h. Significant quercetin concentration-dependent inhibition of protein synthesis and suppression of HIF-1alpha accumulation were observed under hypoxic conditions. Treatment with 100 microM cycloheximide, a protein synthesis inhibitor, replicated the effect of quercetin by inhibiting HIF-1alpha accumulation during hypoxia. These results suggest that suppression of HIF-1alpha accumulation during treatment with quercetin under hypoxic conditions is due to inhibition of protein synthesis. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/18655183/Quercetin_suppresses_hypoxia_induced_accumulation_of_hypoxia_inducible_factor_1alpha__HIF_1alpha__through_inhibiting_protein_synthesis_ L2 - https://doi.org/10.1002/jcb.21851 DB - PRIME DP - Unbound Medicine ER -