Quercetin

Quercetin-induced apoptosis in colorectal tumor cells: possible role of EGF receptor signaling.

Richter M, Ebermann R, Marian B

Institute for Tumor Biology-Cancer Research, University of Vienna, Austria.

Flavonoids are among the best candidates for mediating the protective effect of diets rich in fruits and vegetables with respect to colorectal cancer. To gain additional information about their growth effects on colorectal tumors and their cellular mechanisms of action, a series of related flavonoids was added to cultures of colonic tumor cells. Most compounds induced growth inhibition and cell loss at concentrations of 1-100 microM, relative effectivity being quercetin > apigenin > fisetin > robinetin and kaempferol. Myricetin was only slightly effective. Quercetin was the strongest inducer of apoptosis in a process that was reversible until 10 hours by flavonoid removal and until 24 hours by fetal calf serum. Cells were preferentially retained in the S phase. On the cellular level, quercetin sensitivity was correlated with epidermal growth factor (EGF) receptor levels, rapid growth, and poor differentiation, indicating the possibility of targeting those cells most harmful for the organism. The flavonoid transiently inhibited EGF receptor phosphorylation but had only little effect on other signaling molecules. Even after recovery of receptor phosphorylation, cells remained resistant to EGF stimulation. In summary, the data indicate that inhibition of EGF receptor kinase is an integral part of quercetin-induced growth inhibition, but additional mechanisms also contribute to the overall effect.

PMID: 10453447, UI: 99382819

Dietary intakes of flavonols, flavones and isoflavones by japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration.

Arai Y, Watanabe S, Kimira M, Shimoi K, Mochizuki R, Kinae N

Department of Nutritional Science, Faculty of Applied Bioscience, Tokyo University of Agriculture, Setagaya, Tokyo, 156-8502 Japan and. School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, 422-8526 Japan.

[Medline record in process]

The intake of flavonols, flavones and isoflavones by Japanese women was calculated from our food-phytochemical composition table. The relationship between intake of these phytochemicals and various anthropometric and blood chemistry data was analyzed in a cross-sectional study. The subjects were 115 women volunteers, aged 29-78 y, living in the northern part of Japan. Each subject completed a 3-d dietary record and received a health check up, including urine and blood sampling for biochemical analysis. Total mean intakes of flavonoids (sum of flavonols and flavones) and isoflavones were 16.7 and 47.2 mg/d, respectively. The major source of flavonoids was onions (45.9%) and that of isoflavones was tofu (37.0%). Total intake of isoflavones exceeded that of other dietary antioxidants, such as flavonoids, carotenoids (3.5 mg/d) and vitamin E (8.2 mg/d), and was approximately one half of the vitamin C intake (109 mg/d). The total intake of flavonoids was inversely correlated with the plasma total cholesterol concentration (TC) (r = -0.236, P: < 0.05) and plasma LDL cholesterol concentration (LDL-C) (r = -0.220, P: < 0.05), after the adjustment for age, body mass index and total energy intake. As a single component, quercetin was inversely correlated with both TC (r = -0.261, P: < 0.01) and LDL-C (r = -0. 263, P: < 0.01). Among Japanese, flavonoid and isoflavone intake is the main component among nonnutrient phytochemicals with antioxidant potential in the diet. These results suggest that a high consumption of both flavonoids and isoflavones by Japanese women may contribute to their low incidence of coronary heart disease compared with women in other countries.

PMID: 10958819

Effects of quercetin on the cell growth and the intracellular accumulation and retention of adriamycin.

Asaum J, Matsuzaki H, Kawasak S, Kuroda M, Takeda Y, Kishi K, Hiraki Y

Department of Oral Radiology, Okayama University Dental School, Japan.

In this study, we examined the inhibitory effects on cell growth and the effects of quercetin on intracellular accumulation of adriamycin (ADR) in wild type Ehrlich ascites tumor cells (wild EAT cells) and their ADR-resistant strain. Quercetin strongly inhibited growth in both strains. Cell growth reached a plateau at 3.5 days in the wild type EAT cells and at 7 days in the ADR-resistant strain. The inhibitory concentration in 50% of the ADR-resistant cells on day 7 (24 microM) was twice that of the wild type EAT cells on day 4 (12 microM) after continuous treatment with quercetin. Quercetin decreased the ADR accumulation in the wild type cells but did not affect it in the ADR-resistant cells. Further, quercetin did not affect the retention of ADR in either strain. These results indicated that quercetin decreased ADR accumulation without extruding ADR in the wild type EAT cells. ADR accumulation in the ADR-resistant cells treated with quercetin for 7 days was increased with increasing concentrations of quercetin. Moreover, ADR accumulation in the ADR-resistant cells treated with 50 microM quercetin for 7 days, increased to 186.6% and to 181.9% of that in untreated cells after 60 minutes and 120 minutes incubation, respectively, whilst it increased to 70% from 37.5% of that in the wild type EAT cells after 60 minutes incubation. These findings indicated that quercetin might reverse ADR-resistance.

PMID: 10953314, UI: 20409434

Signal transduction and biochemical targeting of ovarian carcinoma.

Weber G, Shen DF, Li W, Yang H, Look KY, Abonyi M, Prajda N

Indiana University School of Medicine, Indianapolis 46202-5119, USA.

[Medline record in process]

The purpose was to identify novel targets for the chemotherapy of ovarian carcinoma. METHODS: Assays were worked out to measure the activities of P1 kinase, PIP kinase and PLC in ovarian carcinoma samples and in OVCAR-5 cells and to compare the activities to those in normal ovaries. A method was also designed for measuring the concentration of the end product of signal transduction, IP3. RESULTS AND DISCUSSION: Signal transduction activity was markedly increased in ovarian cancer cells as shown by the increased steady-state activities of the three enzymes and the elevated concentrations of IP3. Inhibitors blocked activities of PI kinase (quercetin), PIP kinase (genistein), and lowered GTP concentration required for PLC (tiazofurin). Combinations of tiazofurin with quercetin, tiazofurin with genistein, and quercetin with genistein yielded a synergistic kill of ovarian cancer cells. Tiazofurin, quercetin and genistein are in various stages of clinical trials. CONCLUSION: The increased signal transduction activity provides novel, sensitive targets to chemotherapy in ovarian cancer cells.

PMID: 10949382, UI: 20403658

Nonalcoholic red wine extract and quercetin inhibit LDL oxidation without affecting plasma antioxidant vitamin and carotenoid concentrations.

Chopra M, Fitzsimons PE, Strain JJ, Thurnham DI, Howard AN

Northern Ireland Center for Diet and Health (NICHE), University of Ulster, Coleraine BT52 1SA, Northern Ireland. M.Chopra@ulst.ac.uk

BACKGROUND: Antioxidant enrichment of LDL can increase its resistance to oxidation and hence reduce its atherogenicity. The objective of the present study was to investigate whether in vivo supplementation with nonalcoholic red wine extract and quercetin can increase the oxidative resistance of LDL, and also whether the supplementation has any effect on other antioxidative micronutrients present in the blood. METHODS: Twenty-one male subjects were supplemented with a placebo drink for 2 weeks and randomized into two groups. One group (n = 11) received the red wine extract (1 g/day, equivalent to 375 mL of red wine) and the other group (n = 10) quercetin (30 mg/day) for 2 weeks, followed by a 5-week washout period. RESULTS: In the red wine extract-supplemented group, ex vivo copper-initiated oxidation of LDL (lag phase, mean +/- SD) was 40 +/- 11 min at the baseline, and increased significantly to 47 +/- 6 min [P <0.05 compared with placebo (38 +/- 4 min) and the washout values (40 +/- 5 min)]. In the quercetin-supplemented group, the lag phase was 44 +/- 11 and 40 +/- 5 min for the baseline and placebo, respectively, and increased significantly to 51 +/- 7 min [P <0.05 compared with placebo and washout (41 +/- 9 min)] after supplementation. Plasma lipids (triglycerides, total cholesterol, LDL- and HDL-cholesterol) did not change during the study period. Supplementation with red wine extract or quercetin had no effect on plasma vitamin C and E, retinol, and carotenoid concentrations. CONCLUSIONS: Alcohol-free red wine extract and one of its components, quercetin, can inhibit LDL oxidation after in vivo supplementation; such "inhibition" is unrelated to changes in antioxidant vitamin and carotenoid concentrations.

Publication Types:

Clinical trial

Randomized controlled trial

PMID: 10926898, UI: 20387094

Chemopreventive activity of quercetin during carcinogenesis in cervix uteri in mice.

De S, Chakraborty J, Chakraborty RN, Das S

Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Calcutta - 700 026, India.

[Medline record in process]

The chemopreventive action of quercetin was examined during 20-methyl cholanthrene induced cervical neoplasia in virgin Swiss albino mice. The effects were evaluated on the basis of histopathological observation of the cervical epithelium, micronucleus frequency in vaginal exfoliated cells and some biochemical parameters in the host liver. Quercetin was found to arrest or reverse the progression of cervical neoplasia. The micronucleus frequency was reduced following its administration. The potential anti-carcinogenic effect of quercetin noted in this study is attributed to its antioxidant property which was reflected in the lipid peroxides and their role in the host detoxification system, as expressed in liver glutathione level, glutathione-S-transferase, glutathione peroxidase, catalase and superoxide dismutase activity. As an integral part of the diet quercetin may offer protection to the epithelium from the damaging effects of carcinogenic chemicals. Copyright 2000 John Wiley & Sons, Ltd.

PMID: 10925400, UI: 20385285

Antioxidants and cancer, part 3: quercetin.

Lamson DW, Brignall MS

Bastyr University - Kenmore, WA, USA. davisl@seanet.com

Quercetin is a flavonoid molecule ubiquitous in nature. A number of its actions make it a potential anti-cancer agent, including cell cycle regulation, interaction with type II estrogen binding sites, and tyrosine kinase inhibition. Quercetin appears to be associated with little toxicity when administered orally or intravenously. Much in vitro and some preliminary animal and human data indicate quercetin inhibits tumor growth. More research is needed to elucidate the absorption of oral doses and the magnitude of the anti-cancer effect.

Publication Types:

Review

Review, tutorial

PMID: 10869101, UI: 20328059

Potent inhibitory action of red wine polyphenols on human breast cancer cells.

Damianaki A, Bakogeorgou E, Kampa M, Notas G, Hatzoglou A, Panagiotou S, Gemetzi C, Kouroumalis E, Martin PM, Castanas E

Laboratory of Experimental Endocrinology, University of Crete, School of Medicine and University Hospital, Heraklion, Greece.

Breast cancer (one of the most common malignancy in Western societies), as well as esophagus, stomach, lung, bladder, and prostate cancer, depend on environmental factors and diet for growth and evolution. Dietary micronutriments have been proposed as effective inhibitory agents for cancer initiation, progression, and incidence. Among them, polyphenols, present in different foods and beverages, have retained attention in recent years. Red wine is a rich source of polyphenols, and their antioxidant and tumor arresting effects have been demonstrated in different in vitro and in vivo systems. In the present study, we have measured the antiproliferative effect of red wine concentrate, its total polyphenolic pool, and purified catechin, epicatechin, quercetin, and resveratrol, which account for more than 70% of the total polyphenols in red wine, on the proliferation of hormone sensitive (MCF7, T47D) and resistant (MDA-MB-231) breast cancer cell lines. Our results indicate that polyphenols, at the picomolar or the nanomolar range, decrease cell proliferation in a dose- and a time-dependant manner. In hormone sensitive cell lines, a specific interaction of each polyphenol with steroid receptors was observed, with IC(50)s lower than previously described. Interaction of polyphenols with steroid receptors cannot fully explain their inhibitory effect on cell proliferation. In addition, discrete antioxidant action on each cell line was detected under the same concentrations, both by modifying the toxic effect of H(2)O(2), and the production of reactive oxygen species (ROS), after phorbol ester stimulation. Our results suggest that low concentrations of polyphenols, and consecutively, consumption of wine, or other polyphenol-rich foods and beverages, could have a beneficial antiproliferative effect on breast cancer cell growth. Copyright 2000 Wiley-Liss, Inc.

PMID: 10861841, UI: 20320853

Lipid peroxidation inhibitory activity of some constituents isolated from the stem bark of Eucalyptus globulus.

Yun BS, Lee IK, Kim JP, Chung SH, Shim GS, Yoo ID

Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon.

[Medline record in process]

Twelve compounds with lipid peroxidation inhibitory activity were isolated from the stem bark of E. globulus. Their structures were assigned as a new aromatic monoterpene (1) and eleven known compounds, pinoresinol (2), vomifoliol (3), 3,4,5-trimethoxyphenol 1-O-beta-D-(6'-O-galloyl)glucopyranoside (4), methyl gallate (5), rhamnazin (6), rhamnetin (7), eriodictyol (8), quercetin (9), taxifolin (10), engelitin (11), and catechin (12) on the basis of UV, mass, and NMR spectroscopic analyses. These compounds except vomifoliol significantly inhibited lipid peroxidation in rat liver microsome.

PMID: 10836740, UI: 20294729

Effects of epigallocatechin gallate and quercetin on oxidative damage to cellular DNA.

Johnson MK, Loo G

Graduate Program in Nutrition, The University of North Carolina at Greensboro, Greensboro, NC 27402-6170, USA.

Phenolic phytochemicals are thought to promote optimal health, partly via their antioxidant effects in protecting cellular components against free radicals. The aims of this study were to assess the free radical-scavenging activities of several common phenolic phytochemicals, and then, the effects of the most potent phenolic phytochemicals on oxidative damage to DNA in cultured cells. Epigallocatechin gallate (EGCG) scavenged the stable free radical, alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH), most effectively, while quercetin was about half as effective. Genistein, daidzein, hesperetin, and naringenin did not scavenge DPPH appreciably. Jurkat T-lymphocytes that were pre-incubated with relatively low concentrations of either EGCG or quercetin were less susceptible to DNA damage induced by either a reactive oxygen species or a reactive nitrogen species, as evaluated by the comet assay. More specifically, control cells had a comet score of only 17+/-5, indicating minimal DNA damage. Cells challenged with 25 microM hydrogen peroxide (H(2)O(2)) or 100 microM 3-morpholinosydnonimine (SIN-1, a peroxynitrite generator) had comet scores of 188+/-6 and 125+/-12, respectively, indicating extensive DNA damage. The H(2)O(2)-induced DNA damage was inhibited with 10 microM of either EGCG (comet score: 113+/-23) or quercetin (comet score: 82+/-7). Similarly, the SIN-1-mediated DNA damage was inhibited with 10 microM of either EGCG (comet score: 79+/-13) or quercetin (comet score: 72+/-17). In contrast, noticeable DNA damage was induced in Jurkat T-lymphocytes by incubating with 10-fold higher concentrations (i.e., 100 microM) of either EGCG (comet score: 56+/-17) or quercetin (comet score: 64+/-13) by themselves. Collectively, these data suggest that low concentrations of EGCG and quercetin scavenged free radicals, thereby inhibiting oxidative damage to cellular DNA. But, high concentrations of either EGCG or quercetin alone induced cellular DNA damage.

PMID: 10812333, UI: 20274057

Suppression of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells by chemopreventive agents with a resorcin-type structure.

Mutoh M, Takahashi M, Fukuda K, Matsushima-Hibiya Y, Mutoh H, Sugimura T, Wakabayashi K

Cancer Prevention Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.

Cyclooxygenase-2 (COX-2) is abundantly expressed in colon cancer cells. It has been reported that inhibition of COX-2 enzyme activity is shown to prevent colon carcinogenesis. Thus, suppression of COX-2 expression may also be an effective chemopreventive strategy. In the present study, we constructed a beta-galactosidase reporter gene system in human colon cancer DLD-1 cells, and measured COX-2 promoter-dependent transcriptional activity in the cells. Interferon gamma suppressed this COX-2 promoter activity, while 12-O-tetradecanoylphorbol-13-acetate and transforming growth factor alpha (TGFalpha) exerted enhancing effects. We then tested the influence of 14 candidate cancer chemopreventive compounds on COX-2 promoter activity. Chemopreventive agents such as quercetin, kaempferol, genistein, resveratrol and resorcinol, all having a common resorcin moiety, were found to effectively suppress the COX-2 promoter activity with and without TGFalpha-stimulation in DLD-1 cells. Since all these compounds have a resorcin moiety as a common structure, a resorcin-type structure may play an active role in the inhibition of COX-2 expression in colon cancer cells.

PMID: 10783318, UI: 20247095

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