Quercetin. a Potential Complementary and Alternative Cancer Therapy

Complementary and Alternative Therapies and the Aging Population

Volumn , Issue , 2009, Pages 563-584

  Thangasamy, Thilakavathy ^a   Sittadjody, Sivanandane ^a   Burd, Randy ^a  

^a UNIVERSITY OF ARIZONA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 77953022734     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-0-12-374228-5.00027-5     Document Type: Chapter

References (134)

1. Williams R.J., Spencer J.P., Rice-Evans C. Flavonoids: Antioxidants or signalling molecules?. Free Radic Biol Med 2004, 36:838-849.
2. Graefe E.U., Derendorf H., Veit M. Pharmacokinetics and bioavailability of the flavonol quercetin in humans. Int J Clin Pharmacol Ther 1999, 37:219-233.
3. Alia M., Mateos R., Ramos S., Lecumberri E., Bravo L., Goya L. Influence of quercetin and rutin on growth and antioxidant defense system of a human hepatoma cell line (HepG2). Eur J Nutr 2006, 45:19-28.
4. Elangovan V., Sekar N., Govindasamy S. Chemopreventive potential of dietary bioflavonoids against 20-methylcholanthrene-induced tumorigenesis. Cancer Lett 1994, 87:107-113.
5. De A.W., Mueller-Dieckmann H.J., Schulze-Gahmen U., Worland P.J., Sausville E., Kim S.H. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. Proc Natl Acad Sci USA 1996, 93:2735-2740.
6. Larocca L.M., Teofili L., Maggiano N., Piantelli M., Ranelletti F.O., Leone G. Quercetin and the growth of leukemic progenitors. Leuk Lymphoma 1996, 23:49-53.
7. Agullo G., Gamet-Payrastre L., Manenti S., Viala C., Remesy C., Chap H., Payrastre B. Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: A comparison with tyrosine kinase and protein kinase C inhibition. Biochem Pharmacol 1997, 53:1649-1657.
8. Day A.J., Canada F.J., Diaz J.C., Kroon P.A., Mclauchlan R., Faulds C.B., Plumb G.W., Morgan M.R., Williamson G. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett 2000, 468:166-170.
9. Walle T., Walle U.K., Halushka P.V. Carbon dioxide is the major metabolite of quercetin in humans. J Nutr 2001, 131:2648-2652.
10. Graf B.A., Mullen W., Caldwell S.T., Hartley R.C., Duthie G.G., Lean M.E., Crozier A., Edwards C.A. Disposition and metabolism of [2-14C]quercetin-49-glucoside in rats. Drug Metab Dispos 2005, 33:1036-1043.
11. Graf B.A., Ameho C., Dolnikowski G.G., Milbury P.E., Chen C.Y., Blumberg J.B. Rat gastrointestinal tissues metabolize quercetin. J Nutr 2006, 136:39-44.
12. Walle T., Browning A.M., Steed L.L., Reed S.G., Walle U.K. Flavonoid glucosides are hydrolyzed and thus activated in the oral cavity in humans. J Nutr 2005, 135:48-52.
13. Day A.J., Williamson G. Biomarkers for exposure to dietary flavonoids: A review of the current evidence for identification of quercetin glycosides in plasma. Br J Nutr 2001, 86(Suppl 1):S105-S110.
14. Mullen W., Graf B.A., Caldwell S.T., Hartley R.C., Duthie G.G., Edwards C.A., Lean M.E., Crozier A. Determination of flavonol metabolites in plasma and tissues of rats by HPLC-radiocounting and tandem mass spectrometry following oral ingestion of [2-(14)C]quercetin-4?-glucoside. J Agric Food Chem 2002, 50:6902-6909.
15. Walgren R.A., Walle U.K., Walle T. Transport of quercetin and its glucosides across human intestinal epithelial Caco-2 cells. Biochem Pharmacol 1998, 55:1721-1727.
16. Walgren R.A., Lin J.T., Kinne R.K., Walle T. Cellular uptake of dietary flavonoid quercetin 4?-beta-glucoside by sodium-dependent glucose transporter SGLT1. J Pharmacol Exp Ther 2000, 294:837-843.
17. Salucci M., Stivala L.A., Maiani G., Bugianesi R., Vannini V. Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2). Br J Cancer 2002, 86:1645-1651.
18. Manach C., Williamson G., Morand C., Scalbert A., Remesy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 2005, 81:230S-242S.
19. Shimoi K., Okada H., Furugori M., Goda T., Takase S., Suzuki M., Hara Y., Yamamoto H., Kinae N. Intestinal absorption of luteolin and luteolin 7-O-beta-glucoside in rats and humans. FEBS Lett 1998, 438:220-224.
20. Spencer J.P., Chowrimootoo G., Choudhury R., Debnam E.S., Srai S.K., Rice-Evans C. The small intestine can both absorb and glucuronidate luminal flavonoids. FEBS Lett 1999, 458:224-230.
21. Scalbert A., Williamson G. Dietary intake and bioavailability of polyphenols. J Nutr 2000, 130:2073S-s2085S.
22. Manach C., Morand C., Crespy V., Demigne C., Texier O., Regerat F., Remesy C. Quercetin is recovered in human plasma as conjugated derivatives which retain antioxidant properties. FEBS Lett 1998, 426:331-336.
23. Day A.J., Bao Y., Morgan M.R., Williamson G. Conjugation position of quercetin glucuronides and effect on biological activity. Free Radic Biol Med 2000, 29:1234-1243.
24. Volate S.R., Davenport D.M., Muga S.J., Wargovich M.J. Modulation of aberrant crypt foci and apoptosis by dietary herbal supplements (quercetin, curcumin, silymarin, ginseng and rutin). Carcinogenesis 2005, 26:1450-1456.
25. Dihal A.A., Woutersen R.A., Ommen B.V., Rietjens I.M., Stierum R.H. Modulatory effects of quercetin on proliferation and differentiation of the human colorectal cell line Caco-2. Cancer Lett 2006, 238:248-259.
26. Erlund I., Kosonen T., Alfthan G., Mäenpää J., Perttunen K., Kenraali J., Parantainen J., Aro A. Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. Eur J Clin Pharmacol 2000, 56:545-553.
27. Soleas G.J., Yan J., Goldberg D.M. Measurement of trans-resveratrol, (+)-catechin, and quercetin in rat and human blood and urine by gas chromatography with mass selective detection. Methods Enzymol 2001, 335:130-145.
28. Freireich E.J., Gehan E.A., Rall D.P., Schmidt L.H., Skipper H.E. Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man. Cancer Chemother Rep 1966, 50:219-244.
29. Hollman P.C., van Trijp J.M., Buysman M.N., van der Gaag M.S., Mengelers M.J., de Vries J.H., Katan M.B. Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Lett 1997, 418:152-156.
30. Ferry D.R., Smith A., Malkhandi J., Fyfe D.W., deTakats P.G., Anderson D., Baker J., Kerr D.J. Phase I clinical trial of the flavonoid quercetin: Pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res 1996, 2:659-668.
31. Manach C., Morand C., Texier O., Favier M.L., Agullo G., Demigne C., Regerat F., Remesy C. Quercetin metabolites in plasma of rats fed diets containing rutin or quercetin. J Nutr 1995, 125:1911-1922.
32. Pietta P.G. Flavonoids as antioxidants. J Nat Prod 2000, 63:1035-1042.
33. Murota K., Terao J. Antioxidative flavonoid quercetin: Implication of its intestinal absorption and metabolism. Arch Biochem Biophys 2003, 417:12-17.
34. Robak J., Gryglewski R.J. Flavonoids are scavengers of superoxide anions. Biochem Pharmacol 1988, 37:837-841.
35. Negre-Salvayre A., Salvayre R. Quercetin prevents the cytotoxicity of oxidized LDL on lymphoid cell lines. Free Radic Biol Med 1992, 12:101-106.
36. Filipe P., Haigle J., Silva J.N., Freitas J., Fernandes A., Maziere J.C., Maziere C., Santus R., Morliere P. Anti- and pro-oxidant effects of quercetin in copper-induced low density lipoprotein oxidation. Quercetin as an effective antioxidant against pro-oxidant effects of urate. Eur J Biochem 2004, 271:1991-1999.
37. Alía M., Ramos S., Mateos R., Granado-Serrano A.B., Bravo L., Goya L. Quercetin protects human hepatoma HepG2 against oxidative stress induced by tert-butyl hydroperoxide. Toxicol Appl Pharmacol 2006, 212:110-118.
38. Chang Y.F., Chi C.W., Wang J.J. Reactive oxygen species production is involved in quercetin-induced apoptosis in human hepatoma cells. Nutr Cancer 2006, 55:209.
39. Ferraresi R., Troiano L., Roat E., Lugli E., Nemes E., Nasi M., Pinti M., Fernandez M.I., Cooper E.L., Cossarizza A. Essential requirement of reduced glutathione (GSH) for the anti-oxidant effect of the flavonoid quercetin. Free Radic Res 2005, 39:1249-1258.
40. Formica J.V., Regelson W. Review of the biology of Quercetin and related bioflavonoids. Food Chem Toxicol 1995, 33:1061-1080.
41. Spencer J.P., Kuhnle G.G., Williams R.J., Rice-Evans C. Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites. Biochem J 2003, 372:173-181.
42. Rohrdanz E., Bittner A., Tran-Thi Q.H., Kahl R. The effect of quercetin on the mRNA expression of different antioxidant enzymes in hepatoma cells. Arch Toxicol 2003, 77:506-510.
43. Wilms L.C., Hollman P.C., Boots A.W., Kleinjans J.C. Protection by quercetin and quercetin-rich fruit juice against induction of oxidative DNA damage and formation of BPDE-DNA adducts in human lymphocytes. Mutat Res 2005, 582:155-162.
44. Choi E.J., Chee K.M., Lee B.H. Anti- and prooxidant effects of chronic quercetin administration in rats. Eur J Pharmacol 2003, 482:281-285.
45. Choi E.J., Lee B.H., Lee K., Chee K.M. Long-term combined administration of quercetin and daidzein inhibits quercetin-induced suppression of glutathione antioxidant defenses. Food Chem Toxicol 2005, 43:793-798.
46. Valerio L.G., Kepa J.K., Pickwell G.V., Quattrochi L.C. Induction of human NAD(P)H:quinone oxidoreductase (NQO1) gene expression by the flavonol quercetin. Toxicol Lett 2001, 119:49-57.
47. Thangasamy T., Sittadjody S., Lanza-Jacoby S., Wachsberger P., Limesand K., Burd R. Quercetin selectively inhibits bioreduction and enhances apoptosis in melanoma cells that overexpress tyrosinase. Nutr Cancer 2007, 59:1-11.
48. Gliszczynska-Swiglo A., van der Woude H., de Haan L., Tyrakowska B., Aarts J.M., Rietjens I.M. The role of quinone reductase (NQO1) and quinone chemistry in quercetin cytotoxicity. Toxicol In Vitro 2003, 17:423-431.
49. Boots A.W., Bast A., Haenen G.R. No role of DT-diaphorase (NQO1) in the protection against oxidized quercetin. FEBS Lett 2005, 579:677-682.
50. Asher G., Lotem J., Kama R., Sachs L., Shaul Y. NQO1 stabilizes p53 through a distinct pathway. Proc Natl Acad Sci USA 2002, 99:3099-3104.
51. Asher G., Lotem J., Cohen B., Sachs L., Shaul Y. Regulation of p53 stability and p53-dependent apoptosis by NADH quinone oxidoreductase 1. Proc Natl Acad Sci USA 2001, 98:1188-1193.
52. Anwar A., Dehn D., Siegel D., Kepa J.K., Tang L.J., Pietenpol J.A., Ross D. Interaction of human NAD(P)H:quinone oxidoreductase 1 (NQO1) with the tumor suppressor protein p53 in cells and cell-free systems. J Biol Chem 2003, 278:10368-10373.
53. Nguyen T.T., Tran E., Nguyen T.H., Do P.T., Huynh T.H., Huynh H. The role of activated MEK-ERK pathway in quercetin-induced growth inhibition and apoptosis in A549 lung cancer cells. Carcinogenesis 2004, 25:647-659.
54. Walker E.H., Pacold M.E., Perisic O., Stephens L., Hawkins P.T., Wymann M.P., Williams R.L. Structural determinants of phosphoi-nositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol Cell 2000, 6:909-919.
55. Warngard L., Flodstrom S., Ljungquist S., Ahlborg U.G. Interaction between quercetin, TPA and DDT in the V79 metabolic cooperation assay. Carcinogenesis 1987, 8:1201-1205.
56. Park C.H., Chang J.Y., Hahm E.R., Park S., Kim H.K., Yang C.H. Quercetin, a potent inhibitor against beta-catenin/Tcf signaling in SW480 colon cancer cells. Biochem Biophys Res Commun 2005, 328:227-234.
57. Levine A.J. p53, the cellular gatekeeper for growth and division. Cell 1997, 88:323-331.
58. Kuo P.C., Liu H.F., Chao J.I. Survivin and p53 modulate quercetin-induced cell growth inhibition and apoptosis in human lung carcinoma cells. J Biol Chem 2004, 279:55875-55885.
59. Watjen W., Michels G., Steffan B., Niering P., Chovolou Y., Kampkotter A., Tran-Thi Q.H., Proksch P., Kahl R. Low concentrations of flavonoids are protective in rat H4IIE cells whereas high concentrations cause DNA damage and apoptosis. J Nutr 2005, 135:525-531.
60. Balabhadrapathruni S., Thomas T.J., Yurkow E.J., Amenta P.S., Thomas T. Effects of genistein and structurally related phytoestrogens on cell cycle kinetics and apoptosis in MDA-MB-468 human breast cancer cells. Oncol Rep 2000, 7:3-12.
61. Maggiolini M., Bonofiglio D., Marsico S., Panno M.L., Cenni B., Picard D., Ando S. Estrogen receptor alpha mediates the proliferative but not the cytotoxic dose-dependent effects of two major phytoestrogens on human breast cancer cells. Mol. Pharmacol 2001, 60:595-602.
62. Damianaki A., Bakogeorgou E., Kampa M., Notas G., Hatzoglou A., Panagiotou S., Gemetzi C., Kouroumalis E., Martin P.M., Castanas E. Potent inhibitory action of red wine polyphenols on human breast cancer cells. J Cell Biochem 2000, 78:429-441.
63. Han D.H., Denison M.S., Tachibana H., Yamada K. Relationship between estrogen receptor-binding and estrogenic activities of environmental estrogens and suppression by flavonoids. Biosci Biotechnol Biochem 2002, 66:1479-1487.
64. van der W.H., Gliszczynska-Swiglo A., Struijs K., Smeets A., Alink G.M., Rietjens I.M. Biphasic modulation of cell proliferation by quercetin at concentrations physiologically relevant in humans. Cancer Lett 2003, 200:41-47.
65. Elattar T.M., Virji A.S. The inhibitory effect of curcumin, genistein, quercetin and cisplatin on the growth of oral cancer cells in vitro. Anticancer Res. 2000, 20:1733-1738.
66. Ong C.S., Tran E., Nguyen T.T., Ong C.K., Lee S.K., Lee J.J., Ng C.P., Leong C., Huynh H. Quercetin-induced growth inhibition and cell death in nasopharyngeal carcinoma cells are associated with increase in Bad and hypophosphorylated retinoblastoma expressions. Oncol Rep 2004, 11:727-733.
67. Gupta K., Panda D. Perturbation of microtubule polymerization by quercetin through tubulin binding: A novel mechanism of its antiproliferative activity. Biochemistry 2002, 41:13029-13038.
68. Zhang X.M., Chen J., Xia Y.G., Xu Q. Apoptosis of murine melanoma B16-BL6 cells induced by quercetin targeting mitochondria, inhibiting expression of PKC-alpha and translocating PKC-delta. Cancer Chemother Pharmacol 2005, 55:251-262.
69. Jakubowicz-Gil J., Paduch R., Piersiak T., Glowniak K., Gawron A., Kandefer-Szerszen M. The effect of quercetin on pro-apoptotic activity of cisplatin in HeLa cells. Biochem Pharmacol 2005, 69:1343-1350.
70. Asea A., Ara G., Teicher B.A., Stevenson M.A., Calderwood S.K. Effects of the flavonoid drug quercetin on the response of human prostate tumours to hyperthermia in vitro and in vivo. Int J Hyperthermia 2001, 17:347-356.
71. Gugler R., Leschik M., Dengler H.J. Disposition of quercetin in man after single oral and intravenous doses. Eur J Clin Pharmacol 1975, 9:229-234.
72. Verma A.K., Johnson J.A., Gould M.N., Tanner M.A. Inhibition of 7,12-dimethylbenz(a)anthracene- and N-nitrosomethylurea-induced rat mammary cancer by dietary flavonol quercetin. Cancer Res 1988, 48:5754-5758.
73. Molnar J., Beladi I., Domonkos K., Foldeak S., Boda K., Veckenstedt A. Antitumor activity of flavonoids on NK/Ly ascites tumor cells. Neoplasma 1981, 28:11-18.
74. Ferrer P., Asensi M., Segarra R., Ortega A., Benlloch M., Obrador E., Varea M.T., Asensio G., Jorda L., Estrela J.M. Association between pterostilbene and quercetin inhibits metastatic activity of B16 melanoma. Neoplasia 2005, 7:37-47.
75. Femia A.P., Caderni G., Ianni M., Salvadori M., Schijlen E., Collins G., Bovy A., Dolara P. Effect of diets fortified with tomatoes or onions with variable quercetin-glycoside content on azoxymethane-induced aberrant crypt foci in the colon of rats. Eur J Nutr 2003, 42:346-352.
76. Lamson D.W., Brignall M.S. Antioxidants and cancer, part 3: Quercetin. Altern Med Rev 2000, 5:196-208.
77. Debes A., Oerding M., Willers R., Gobel U., Wessalowski R. Sensitization of human Ewing's tumor cells to chemotherapy and heat treatment by the bioflavonoid quercetin. Anticancer Res 2003, 23:3359-3366.
78. Mutoh M., Takahashi M., Fukuda K., Komatsu H., Enya T., Matsushima-Hibiya Y., Mutoh H., Sugimura T., Wakabayashi K. Suppression by flavonoids of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells: Structure-activity relationship. Jpn J Cancer Res 2000, 91:686-691.
79. Raso G.M., Meli R., Di C.G., Pacilio M., Di C.R. Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by flavonoids in macrophage J774A.1. Life Sci 2001, 68:921-931.
80. Jones D.J., Lamb J.H., Verschoyle R.D., Howells L.M., Butterworth M., Lim C.K., Ferry D., Farmer P.B., Gescher A.J. Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity. Br J Cancer 2004, 91:1213-1219.
81. Moon J.H., Tsushida T., Nakahara K., Terao J. Identification of quercetin 3-O-beta-D-glucuronide as an antioxidative metabolite in rat plasma after oral administration of quercetin. Free Radic Biol Med 2001, 30:1274-1285.
82. Wittig J., Herderich M., Graefe E.U., Veit M. Identification of quercetin glucuronides in human plasma by high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Biomed Sci Appl 2001, 753:237-243.
83. Young J.F., Nielsen S.E., Haraldsdottir J., Daneshvar B., Lauridsen S.T., Knuthsen P., Crozier A., Sandstrom B., Dragsted L.O. Effect of fruit juice intake on urinary quercetin excretion and biomarkers of antioxidative status. Am J Clin Nutr 1999, 69:87-94.
84. Kim H.Y., Kim O.H., Sung M.K. Effects of phenol-depleted and phenol-rich diets on blood markers of oxidative stress, and urinary excretion of quercetin and kaempferol in healthy volunteers. J Am Coll Nutr 2003, 22:217-223.
85. Radtke J., Linseisen J., Wolfram G. Fasting plasma concentrations of selected flavonoids as markers of their ordinary dietary intake. Eur J Nutr 2002, 41:203-209.
86. Morand C., Crespy V., Manach C., Besson C., Demigne C., Remesy C. Plasma metabolites of quercetin and their antioxidant properties. Am J Physiol 1998, 275:R212-R219.
87. Conquer J.A., Maiani G., Azzini E., Raguzzini A., Holub B.J. Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects. J Nutr 1998, 128:593-597.
88. Ishii K., Furuta T., Kasuya Y. High-performance liquid chromatographic determination of quercetin in human plasma and urine utilizing solid-phase extraction and ultraviolet detection. J Chromatogr B Analyt Technol Biomed Life Sci 2003, 794:49-56.
89. Okamoto T. Safety of quercetin for clinical application (Review). Int J Mol Med 2005, 16:275-278.
90. Silberberg M., Morand C., Manach C., Scalbert A., Remesy C. Co-administration of quercetin and catechin in rats alters their absorption but not their metabolism. Life Sci 2005, 77:3156-3167.
91. Pamukcu A.M., Yalciner S., Hatcher J.F., Bryan G.T. Quercetin, a rat intestinal and bladder carcinogen present in bracken fern (Pteridium aquilinum). Cancer Res 1980, 40:3468-3472.
92. Ambrose A.M., Robbins D.J., Deeds F. Comparative toxicities of quercetin and quercitrin. J Am Pharm Assoc 1952, 41:119-122.
93. Matsukawa Y., Nishino H., Okuyama Y., Matsui T., Matsumoto T., Matsumura S., Shimizu Y., Sowa Y., Sakai T. Effects of quercetin and/or restraint stress on formation of aberrant crypt foci induced by azoxymethane in rat colons. Oncology 1997, 54:118-121.
94. Hirono I., Ueno I., Hosaka S., Takanashi H., Matsushima T., Sugimura T., Natori S. Carcinogenicity examination of quercetin and rutin in ACI rats. Cancer Lett 1981, 13:15-21.
95. Sankarasharma D., Ganapathy V., Shyamaladevi C.S. Suppression of tumor growth and invasion in 9,10 dimethyl benz(a) anthracene induced mammary carcinoma by the plant bioflavonoid quercetin. Chem Biol Interact 2006, 162:106-113.
96. Gee J.M., Hara H., Johnson I.T. Suppression of intestinal crypt cell proliferation and aberrant crypt foci by dietary quercetin in rats. Nutr Cancer 2002, 43:193-201.
97. Castillo M.H., Perkins E., Campbell J.H., Doerr R., Hassett J.M., Kandaswami C., Middleton E. The effects of the bioflavonoid quercetin on squamous cell carcinoma of head and neck origin. Am J Surg 1989, 158:351-355.
98. Morino K., Matsukara N., Kawachi T., Ohgaki H., Sugimura T., Hirono I. Carcinogenicity test of quercetin and rutin in golden hamsters by oral administration. Carcinogenesis 1982, 3:93-97.
99. van Erk M.J., Roepman P., van der Lende T.R., Stierum R.H., Aarts J.M., van Bladeren P.J., van Ommen B. Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr 2005, 44:143-156.
100. Ranelletti F.O., Maggiano N., Serra F.G., Ricci R., Larocca L.M., Lanza P., Scambia G., Fattorossi A., Capelli A., Piantelli M. Quercetin inhibits p21-RAS expression in human colon cancer cell lines and in primary colorectal tumors. Int J Cancer 2000, 85:438-445.
101. Yang J.H., Hsia T.C., Kuo H.M., Lee Chao P.D., Chou C.C., Wei Y.H., Chung J.G. Inhibition of lung cancer cell growth by quercetin glucuronides via G2/M arrest and induction of apoptosis. Drug Metab Dispos 2006, 34:296-304.
102. Son Yo., Kook S.H., Choi K.C., Jang Y.S., Jeon Y.M., Lee K.Y., Kim J., Chung M.S., Chung G.H., Lee J.C. Quercetin, a bioflavonoid, accelerates TNF-alpha-induced growth inhibition and apoptosis in MC3T3-E1 osteoblastic cells. Eur J Pharmacol 2006, 529:24-32.
103. Lee T.J., Kim O.H., Kim Y.H., Lim J.H., Kim S., Park J.W., Kwon T.K. Quercetin arrests G2/M phase and induces caspase-dependent cell death in U937 cells. Cancer Lett 2006, 240:234-242.
104. Brisdelli F., Coccia C., Cinque B., Cifone M.G., Bozzi A. Induction of apoptosis by quercetin: Different response of human chronic myeloid (K562) and acute lymphoblastic (HSB-2) leukemia cells. Mol Cell Biochem 2007, 296:137-149.
105. Mu C., Jia P., Yan Z., Liu X., Li X., Liu H. Quercetin induces cell cycle G1 arrest through elevating Cdk inhibitors p21 and p27 in human hepatoma cell line (HepG2). Methods Find Exp Clin Pharmacol 2007, 29:179-183.
106. Granado-Serrano A.B., Martín M.A., Bravo L., Goya L., Ramos S. Quercetin induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI-3-kinase/Akt and ERK pathways in a human hepatoma cell line (HepG2). J Nutr 2006, 136:2715-2721.
107. Kim W.K., Bang M.H., Kim E.S., Kang N.E., Jung K.C., Cho H.J., Park J.H. Quercetin decreases the expression of ErbB2 and ErbB3 proteins in HT-29 human colon cancer cells. J Nutr Biochem 2005, 16:155-162.
108. Horvathova K., Novotny L., Tothova D., Vachalkova A. Determination of free radical scavenging activity of quercetin, rutin, luteolin and apigenin in H2O2-treated human ML cells K562. Neoplasma 2004, 51:395-399.
109. Robaszkiewicz A., Balcerczyk A., Bartosz G. Antioxidative and prooxidative effects of quercetin on A549 cells. Cell Biol Int 2007, 31:1245-1250.
110. Yoshida M., Sakai T., Hosokawa N., Marui N., Matsumoto K., Fujioka A., Nishino H., Aoike A. The effect of quercetin on cell cycle progression and growth of human gastric cancer cells. FEBS Lett 1990, 260:10-13.
111. Triantafyllou A., Liakos P., Tsakalof A., Chachami G., Paraskeva E., Molyvdas P.A., Georgatsou E., Simos G., Bonanou S. The flavonoid quercetin induces hypoxia-inducible factor-1alpha (HIF-1alpha) and inhibits cell proliferation by depleting intracellular iron. Free Radic Res 2007, 41:342-356.
112. Avila M.A., Velasco J.A., Cansado J., Notario V. Quercetin mediates the down-regulation of mutant p53 in the human breast cancer cell line MDA-MB468. Cancer Res 1994, 54:2424-2428.
113. McAnlis G.T., McEneny J., Pearce J., Young I.S. Absorption and antioxidant effects of quercetin from onions, in man. Eur J Clin Nutr 1999, 53:92-96.
114. Aziz A.A., Edwards C.A., Lean M.E., Crozier A. Absorption and excretion of conjugated flavonols, including quercetin-4'-O-beta-glucoside and isorhamnetin-4'-O-beta-glucoside by human volunteers after the consumption of onions. Free Radic Res 1998, 29:257-269.
115. de Vries J.H., Hollman P.C., Meyboom S., Buysman M.N., Zock P.L., van Staveren W.A., Katan M.B. Plasma concentrations and urinary excretion of the antioxidant flavonols quercetin and kaempferol as biomarkers for dietary intake. Am J Clin Nutr 1998, 68:60-65.
116. Hollman P.C., vd G.M., Mengelers M.J., van Trijp J.M., de Vries J.H., Katan M.B. Absorption and disposition kinetics of the dietary antioxidant quercetin in man. Free Radic Biol Med 1996, 21:703-707.
117. Graefe E.U., Wittig J., Mueller S., Riethling A.K., Uehleke B., Drewelow B., Pforte H., Jacobasch G., Derendorf H., Veit M. Pharmacokinetics and bioavailability of quercetin glycosides in humans. J Clin Pharmacol 2001, 41:492-499.
118. Dávalos A., Castilla P., Gómez-Cordovés C., Bartolomé B. Quercetin is bioavailable from a single ingestion of grape juice. Int J Food Sci Nutr 2006, 57:391-398.
119. Janssen K., Mensink R.P., Cox F.J., Harryvan J.L., Hovenier R., Hollman P.C., Katan M.B. Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: Results from an in vitro and a dietary supplement study. Am J Clin Nutr 1998, 67:255-262.
120. Moon J.H., Nakata R., Oshima S., Inakuma T., Terao J. Accumulation of quercetin conjugates in blood plasma after the short-term ingestion of onion by women. Am J Physiol Regul Integr Comp Physiol 2000, 279:R461-R467.
121. Murota K., Hotta A., Ido H., Kawai Y., Moon J.H., Sekido K., Hayashi H., Inakuma T., Terao J. Antioxidant capacity of albumin-bound quercetin metabolites after onion consumption in humans. J Med Invest 2007, 54:370-374.
122. Olthof M.R., Hollman P.C., Vree T.B., Katan M.B. Bioavailabilities of quercetin-3-glucoside and quercetin-4'-glucoside do not differ in humans. J Nutr 2000, 130:1200-1203.
123. Hollman P.C., Katan M.B. Health effects and bioavailability of dietary flavonols. Free Radic Res 1999, 31(Suppl):S75-S80.
124. Boyle S.P., Dobson V.L., Duthie S.J., Hinselwood D.C., Kyle J.A., Collins A.R. Bioavailability and efficiency of rutin as an antioxidant: A human supplementation study. Eur J Clin Nutr 2000, 54:774-782.
125. Graefe E.U., Wittig J., Mueller S., Riethling A.K., Uehleke B., Drewelow B., Pforte H., Jacobasch G., Derendorf H., Veit M. Pharmacokinetics and bioavailability of quercetin glycosides in humans. J Clin Pharmacol 2001, 41:492-499.
126. Liu G.A., Zheng R.L. Protection against damaged DNA in the single cell by polyphenols. Pharmazie 2002, 57:852-854.
127. 2-induced chromosomal damage to WIL2-NS cells. Biosci Biotechnol Biochem 2004, 68:271-276.
128. Spencer J.P., Rice-Evans C., Williams R.J. Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability. J Biol Chem 2003, 278:34783-34793.
129. Shen S.C., Chen Y.C., Hsu F.L., Lee W.R. Differential apoptosis-inducing effect of quercetin and its glycosides in human promyeloleukemic HL-60 cells by alternative activation of the caspase 3 cascade. J Cell Biochem 2003, 89:1044-1055.
130. Yen G.C., Duh P.D., Tsai H.L., Huang S.L. Pro-oxidative properties of flavonoids in human lymphocytes. Biosci Biotechnol Biochem 2003, 67:1215-1222.
131. Makris D.P., Rossiter J.T. Comparison of quercetin and a non-orthohydroxy flavonol as antioxidants by competing in vitro oxidation reactions. J Agric Food Chem 2001, 49:3370-3377.
132. Rao Y.K., Geethangili M., Fang S.H., Tzeng Y.M. Antioxidant and cytotoxic activities of naturally occurring phenolic and related compounds: A comparative study. Food Chem Toxicol 2007, 45:1770-1776.
133. Awad H.M., Boersma M.G., Vervoort J., Rietjens I.M. Peroxidase-catalyzed formation of quercetin quinone methide-glutathione adducts. Arch Biochem Biophys 2000, 378:224-233.
134. Metodiewa D., Jaiswal A.K., Cenas N., Dickancaite E., Segura-Aguilar J. Quercetin may act as a cytotoxic prooxidant after its metabolic activation to semiquinone and quinoidal product. Free Radic Biol Med 1999, 26:107-116.