![Sample our Physical Sciences journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/110819/TOC-Subject-Sample-2021-Physical-Sciences.jpg"})
Abstract
Quercetin, a flavonoid with anti-oxidant, metal chelating, kinase modulating and anti-proliferative properties, can induce hypoxia-inducible factor-1α (HIF-1α) in normoxia, but its mechanism of action has not been determined. In this study we characterized the induction of HIF-1α and the inhibition of cell proliferation caused by quercetin in HeLa and ASM (airway smooth muscle) cells and examined the effect of iron on these processes. Furthermore, we investigated the relevance of the intracellular levels of quercetin to HIF-1α expression and cell proliferation. Our data demonstrate that quercetin depletes intracellular calcein–chelatable iron and that supplying additional iron from extracellular or intracellular pools abrogates the induction of HIF-1α by quercetin. Moreover, addition of iron reverses the quercetin-induced inhibition of DNA synthesis, cell proliferation and cycle progression, but to different extents, depending on cell type. We propose that quercetin stabilises HIF-1α and inhibits cell proliferation predominantly by decreasing the concentration of intracellular iron through chelation.
| Abbreviations | ||
| DFO | = | desferrioxamine |
| HRE | = | hypoxia-response-element |
| HIF | = | hypoxia-inducible factor |
| MAPK | = | mitogen activated protein kinase |
| N-acetyl-l-cysteine | = | NAC |
| PHD | = | prolyl hydoxylase domain protein |
| PI-3K | = | phosphatidylinositol-3 kinase |
| ROS | = | reactive oxygen species |
| Abbreviations | ||
| DFO | = | desferrioxamine |
| HRE | = | hypoxia-response-element |
| HIF | = | hypoxia-inducible factor |
| MAPK | = | mitogen activated protein kinase |
| N-acetyl-l-cysteine | = | NAC |
| PHD | = | prolyl hydoxylase domain protein |
| PI-3K | = | phosphatidylinositol-3 kinase |
| ROS | = | reactive oxygen species |