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The antioxidant quercetin inhibits cellular proliferation via HIF-1-dependent induction of p21WAF.
Antioxid Redox Signal. 2010 Aug 15; 13(4):437-48.AR

Abstract

Flavonoids are dietary antioxidants that may play a role as adjunct nutritional supplements in cancer or during inflammatory disorders. Hypoxia and the transcription factor hypoxia-inducible factor-1alpha also appear to play a key role in many human cancers. In this study, we investigated the role of quercetin in the hypoxia-dependent HIF-1alpha induction. It was shown that quercetin induced HIF-1alpha expression and HIF-1 activity under normoxia and hypoxia in human HepG2 hepatoma cells. By using actinomycin D and cycloheximide, we showed that quercetin acted post-transcriptionally by prolonging the HIF-1alpha protein half-life. Thereby quercetin interfered with the proline hydroxylation-dependent HIF-1alpha protein destabilization in the N-terminal HIF-1alpha transactivation domain. Experiments with quercetin analogues revealed that a flavonol structure and the presence of hydroxyl groups at position 3' and 4' are a prerequisite for the HIF-1alpha stabilizing effects. Further, quercetin inhibited cell proliferation and induced expression of the cell cycle inhibitor p21WAF and knocking-down HIF-1alpha disrupted these effects. These results provide evidence that quercetin inhibits the cell cycle and that induction of the HIF-system contributes to these effects of quercetin.

Authors+Show Affiliations

Department of Chemistry, University of Kaiserslautern , Kaiserslautern, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19958256

Citation

Bach, Aline, et al. "The Antioxidant Quercetin Inhibits Cellular Proliferation Via HIF-1-dependent Induction of P21WAF." Antioxidants & Redox Signaling, vol. 13, no. 4, 2010, pp. 437-48.
Bach A, Bender-Sigel J, Schrenk D, et al. The antioxidant quercetin inhibits cellular proliferation via HIF-1-dependent induction of p21WAF. Antioxid Redox Signal. 2010;13(4):437-48.
Bach, A., Bender-Sigel, J., Schrenk, D., Flügel, D., & Kietzmann, T. (2010). The antioxidant quercetin inhibits cellular proliferation via HIF-1-dependent induction of p21WAF. Antioxidants & Redox Signaling, 13(4), 437-48. https://doi.org/10.1089/ars.2009.3000
Bach A, et al. The Antioxidant Quercetin Inhibits Cellular Proliferation Via HIF-1-dependent Induction of P21WAF. Antioxid Redox Signal. 2010 Aug 15;13(4):437-48. PubMed PMID: 19958256.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The antioxidant quercetin inhibits cellular proliferation via HIF-1-dependent induction of p21WAF. AU - Bach,Aline, AU - Bender-Sigel,Julia, AU - Schrenk,Dieter, AU - Flügel,Daniela, AU - Kietzmann,Thomas, PY - 2009/12/5/entrez PY - 2009/12/5/pubmed PY - 2010/10/1/medline SP - 437 EP - 48 JF - Antioxidants & redox signaling JO - Antioxid Redox Signal VL - 13 IS - 4 N2 - Flavonoids are dietary antioxidants that may play a role as adjunct nutritional supplements in cancer or during inflammatory disorders. Hypoxia and the transcription factor hypoxia-inducible factor-1alpha also appear to play a key role in many human cancers. In this study, we investigated the role of quercetin in the hypoxia-dependent HIF-1alpha induction. It was shown that quercetin induced HIF-1alpha expression and HIF-1 activity under normoxia and hypoxia in human HepG2 hepatoma cells. By using actinomycin D and cycloheximide, we showed that quercetin acted post-transcriptionally by prolonging the HIF-1alpha protein half-life. Thereby quercetin interfered with the proline hydroxylation-dependent HIF-1alpha protein destabilization in the N-terminal HIF-1alpha transactivation domain. Experiments with quercetin analogues revealed that a flavonol structure and the presence of hydroxyl groups at position 3' and 4' are a prerequisite for the HIF-1alpha stabilizing effects. Further, quercetin inhibited cell proliferation and induced expression of the cell cycle inhibitor p21WAF and knocking-down HIF-1alpha disrupted these effects. These results provide evidence that quercetin inhibits the cell cycle and that induction of the HIF-system contributes to these effects of quercetin. SN - 1557-7716 UR - https://www.unboundmedicine.com/medline/citation/19958256/The_antioxidant_quercetin_inhibits_cellular_proliferation_via_HIF_1_dependent_induction_of_p21WAF_ L2 - https://www.liebertpub.com/doi/10.1089/ars.2009.3000?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -