Disease relevance of quercetin

• Using published food-composition data for flavonoids, we found an inverse association between intake of quercetin and risk of lung cancer (P for trend =.07) that appears consistent with associations for its food sources [1].
• We previously reported that quercetin and some other flavonoids inhibited the induction of HSPs in HeLa and COLO 320DM cells, derived from a human colon cancer, at the level of mRNA accumulation [2].
• In the HuH7 human hepatoma cell line, PON-1 activity and mRNA levels were increased by dietary polyphenolic compounds such as quercetin but also by toxic ligands of the aryl hydrocarbon receptor (AhR) such as 3-methylcholanthrene (3-MC) [3].
• We show here that quercetin inhibits the clonogenic activity of 20 of 22 acute leukemias (AL; 4 M1-AML, 3 M2-AML, 2 M3-AML, 3 M4-AML, 3 M5-AML, and 7 ALL) [4].
• Dietary quercetin did not elicit any detectable sign of toxicity [5].
• Taken together, the results of the present study suggest that quercetin sensitizes glioma cells to death-receptor-mediated apoptosis by suppression of inhibitor of the apoptosis protein survivin [6].

Psychiatry related information on quercetin

• Quercetin-fed mice showed higher activity upon induction by new environmental stimuli, lower anxiety and higher novelty-seeking behavior in the open field tasks, and significantly improved learning and memory ability in step-through and Morris water Maze tests compared with D-gal-treated mice [7].
• Because quercetin, a natural flavonoid, is known to scavenge free radicals, we investigated whether quercetin attenuates white matter damage in rats with chronic cerebral hypoperfusion, as a model of vascular dementia [8].
• Peristaltic motor activity suppressed by quercetin (300 micromol/l), but not genistein (100 micromol/l), was partially restored by apamin [9].
• An i.m. administration of various doses of quercetin admixed with 1.0 mg of MCA, however, significantly shortened the mean latency periods for the development of local primary tumors compared with those of the group which had been given MCA alone [10].
• Although several recent studies found that both SJ and Ginkgo biloba have the same components of quercetin and rutin, only Ginkgo biloba has been widely used to treat cerebrovascular disorders and dementia in humans [11].

High impact information on quercetin

• The X-ray crystallographic structures of PI3Kgamma bound to these lipid kinase inhibitors and to the broad-spectrum protein kinase inhibitors quercetin, myricetin, and staurosporine reveal how these compounds fit into the ATP binding pocket [12].
• The partial inhibition of Na+-, K+- ATPase activity by quercetin observed in tumor cells was confirmed in thymocyte plasma membranes [13].
• Inhibition of PtdIns(4,5)P2 synthesis by quercetin or phenylarsine oxide prevented the relocalization of the fluorescent probe to the membranes after Ca2+ chelation in ionomycin-treated cells or during agonist stimulation [14].
• The x-ray structures of Aspergillus japonicus 2,3QD anaerobically complexed with the substrate kaempferol and the natural substrate quercetin have been determined at 1.90- and 1.75-A resolution, respectively [15].
• Addition of quercetin (0.1 mM) and trans-flupenthixol (0.2 mM), inhibitors of nuclear protein kinase II and calmodulin-dependent kinase, respectively, inhibited the synthesis of vitellogenin mRNA by about 55% without affecting total RNA synthesis [16].

Chemical compound and disease context of quercetin

• A single topical application of tannic acid, quercetin, myricetin, and anthraflavic acid at a dose of 400 mumol/kg body weight resulted in the inhibition of [3H]benzo(a)pyrene binding to epidermal DNA (48-73%) and protein (51-63%) [17].
• The effects of the bioflavonoid quercetin (3,3',4',5,7-pentahydroxyflavone) on the growth and cell cycle progression of the human breast cancer cell line MDA-MB468 have been studied [18].
• Quercetin (3,3',4',5,7-pentahydroxyflavone) entrapped within phospholipid vesicles inhibited [3H]thymidine incorporation and lactate production in Ehrlich ascites tumor cells [19].
• Effect of liposome-encapsulated quercetin on DNA synthesis, lactate production, and cyclic adenosine 3':5'-monophosphate level in Ehrlich ascites tumor cells [19].
• When diabetic rats were administered glucose with quercetin, hyperglycemia was significantly decreased compared with administration of glucose alone [20].

Biological context of quercetin

• Quercetin inhibited heat-induced CAT activity in COS-7 and COLO 320DM cells which were transfected with plasmids bearing the CAT gene under the control of the promoter region of the human HSP70 gene [2].
• (2) Similar concentrations of quercetin inhibited respiratory burst activity of the cells as measured by oxygen consumption, glucose oxidation, or iodination of protein [21].
• Induction of apoptosis by quercetin: involvement of heat shock protein [22].
• Quercetin inhibited cell proliferation with an IC50 (a drug concentration which inhibited growth by 50% following a 3-day exposure) value of 7 micrograms/ml [18].
• Quercetin reversibly blocked the cell cycle at a point 3-6 h before the start of DNA synthesis [23].

Anatomical context of quercetin

• Quercetin inhibits Ca2+ uptake but not Ca2+ release by sarcoplasmic reticulum in skinned muscle fibers [24].
• The bioflavinoid quercetin was found to exert at least three separate effects on human polymorphonuclear leukocytes [21].
• These results obtained by elutriation were confirmed by pharmacologically inducing cell cycle arrest in proliferating lymphoid cell lines with hydroxyurea, quercetin, and nocodazole which blocked cells at S, G2, and M phases, respectively [25].
• When HeLa cells were exposed to quercetin at 41 and 42 degrees, significant potentiation of hyperthermia-induced cytotoxicity was observed [26].
• The 50% inhibitory concentrations for tannic acid, myricetin, quercetin, and anthraflavic acid ranged from 4.4 X 10(-5) M to 12.4 X 10(-5) M in microsomes prepared from control and 3-methylcholanthrene-pretreated animals [27].

Associations of quercetin with other chemical compounds

• Effects of quercetin on magnesium-dependent adenosine triphosphatase and the metabolism of human polymorphonuclear leukocytes [21].
• Treatment with quercetin inhibited the binding of HSF to the HSE in whole-cell extracts activated in vivo by heat shock and in cytoplasmic extracts activated in vitro by elevated temperature or by urea [2].
• The effect of quercetin, a flavonoid found in many plants, on the proliferation of human leukemic T-cells was analyzed [23].
• The effects of dietary supplementation of flavonol quercetin on both 7,12-dimethylbenz(a)anthracene (DMBA)- and N-nitrosomethylurea-induced mammary cancer in female Sprague-Dawley rats were determined [5].
• Quercetin, an inhibitor of lactate transport and a hyperthermic sensitizer of HeLa cells [26].
• HO-1 up-regulation by quercetin protected human hepatocytes from ethanol-induced oxidative stress [28].
• The quercetin studies thus reveal that the phospholipase-A(2)/lipoxygenase pathway appears to play an important role in TSH regulation of NIS gene expression, whereas quercetin inhibition of growth appears to involve an effect on insulin/IGF-I-Akt signaling [29].

Gene context of quercetin

• John's wort (Hypericum perforatum) preparations and some of their main constituents (hypericin, pseudohypericin, hyperforin, rutin, and quercetin) were examined for their potential to inhibit carcinogen activation by human cytochrome P450 1A1 (CYP1A1) [30].
• Survivin and p53 modulate quercetin-induced cell growth inhibition and apoptosis in human lung carcinoma cells [31].
• Furthermore, transfection of a small interfering RNA of p21 enhanced the quercetin-induced cell death in A549 cells [31].
• In contrast, neither quercetin nor its O-methylated metabolites had any measurable effect on c-Jun N-terminal kinase phosphorylation [32].
• O-Methylated quercetin metabolites inhibited Akt/PKB to lesser extent and did not induce such strong activation of caspase-3, which was reflected in the lower amount of damage they inflicted on neurons [32].

Analytical, diagnostic and therapeutic context of quercetin

• In this study, we examined the effects of quercetin on the induction of HSP70 promoter-regulated chloramphenicol acetyltransferase (CAT) activity and on the binding of HSF to the heat shock element (HSE) by a gel mobility shift assay with extracts of COLO 320DM cells [2].
• The synthesis of HSP70 was inhibited by quercetin when determined by immunocytochemistry, Western blot analysis, and Northern blot analysis [22].
• Agarose gel electrophoresis of quercetin-treated tumor cells demonstrated a typical ladder-like pattern of DNA fragments [22].
• Biodistribution of liposomal quercetin i.v. at 50 mg/kg in tumor-bearing mice was detected by high-performance liquid chromatography [33].
• This is, to our knowledge, the first evidence that Q3GA accumulates in vivo after oral administration of quercetin [34].

References