Cancer Letters
Volume 238, Issue 2 , Pages 248-259 , 18 July 2006

Modulatory effects of quercetin on proliferation and differentiation of the human colorectal cell line Caco-2

  • Ashwin A. Dihal

      Affiliations

    • Physiological Sciences Department, TNO Quality of Life, Zeist, The Netherlands
    • Division of Toxicology, Wageningen University, Wageningen, The Netherlands
    • Corresponding Author InformationCorresponding author. Physiological Sciences Department, TNO Quality of Life, P.O. Box 360, Postpunt 8, 3700 AJ Zeist, The Netherlands. Tel.: +31 30 6944193; fax: +31 30 6960264.
    • ,
  • Ruud A. Woutersen

      Affiliations

    • Department of Toxicology and Applied Pharmacology, TNO Quality of Life, Zeist, The Netherlands
    • ,
  • Ben van Ommen

      Affiliations

    • Physiological Sciences Department, TNO Quality of Life, Zeist, The Netherlands
    • ,
  • Ivonne M.C.M. Rietjens

      Affiliations

    • Division of Toxicology, Wageningen University, Wageningen, The Netherlands
    • ,
  • Rob H. Stierum

      Affiliations

    • Physiological Sciences Department, TNO Quality of Life, Zeist, The Netherlands

Received 26 May 2005 ,Revised 8 July 2005 ,Accepted 10 July 2005.

References 

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: globocan 2000. Int. J. Cancer. 2001;94:153–156
  2. Fodde R, Smits R, Clevers H. APC, signal transduction and genetic instability in colorectal cancer. Nat. Rev. Cancer. 2001;1:55–67
  3. Stierum R, Gaspari M, Dommels Y, Ouatas T, Pluk H, Jespersen S, et al. Proteome analysis reveals novel proteins associated with proliferation and differentiation of the colorectal cancer cell line Caco-2. Biochim. Biophys. Acta. 2003;1650:73–91
  4. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70
  5. Fodde R. The APC gene in colorectal cancer. Eur. J. Cancer. 2002;38:867–871
  6. Bingham SA, Day NE, Luben R, Ferrari P, Slimani N, Norat T, et al. European Prospective Investigation into Cancer and Nutrition, Dietary fibre in food and protection against colorectal cancer in the European prospective investigation into cancer and nutrition (EPIC): an observational study. Lancet. 2003;361:1496–1501
  7. Knekt P, Jarvinen R, Seppanen R, Hellovaara M, Teppo L, Pukkala E, et al. Dietary flavonoids and the risk of lung cancer and other malignant neoplasms. Am. J. Epidemiol. 1997;146:223–230
  8. Schoen RE. The case for population-based screening for colorectal cancer. Nat. Rev. Cancer. 2002;2:65–70
  9. Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. Polyphenols: food sources and bioavailability. Am. J. Clin. Nutr. 2004;79:727–747
  10. Day AJ, DuPont MS, Ridley S, Rhodes M, Rhodes MJ, Morgan MR, et al. Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver beta-glucosidase activity. FEBS Lett. 1998;436:71–75
  11. Kim DH, Jung EA, Sohng IS, Han JA, Kim TH, Han MJ. Intestinal bacterial metabolism of flavonoids and its relation to some biological activities. Arch. Pharm. Res. 1998;21:17–23
  12. Hollman PC, de Vries JH, van Leeuwen SD, Mengelers MJ, Katan MB. Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am. J. Clin. Nutr. 1995;62:1276–1282
  13. Jones DJ, Lamb JH, Verschoyle RD, Howells LM, Butterworth M, Lim CK, et al. Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity. Br. J. Cancer. 2004;91:1213–1219
  14. Day AJ, Bao Y, Morgan MR, Williamson G. Conjugation position of quercetin glucuronides and effect on biological activity. Free Radic. Biol. Med. 2000;29:1234–1243
  15. Avila MA, Velasco JA, 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
  16. Tanaka T, Kawabata K, Honjo S, Kohno H, Murakami M, Shimada R, et al. Inhibition of azoxymethane-induced aberrant crypt foci in rats by natural compounds, caffeine, quercetin and morin. Oncol. Rep. 1999;6:1333–1340
  17. Murota K, Terao J. Antioxidative flavonoid quercetin: implication of its intestinal absorption and metabolism. Arch. Biochem. Biophys. 2003;417:12–17
  18. Kuo SM. Antiproliferative potency of structurally distinct dietary flavonoids on human colon cancer cells. Cancer Lett. 1996;110:41–48
  19. van der Woude H, Gliszczynska-Swiglo A, Struijs K, Smeets A, Alink GM, Rietjens IM. Biphasic modulation of cell proliferation by quercetin at concentrations physiologically relevant in humans. Cancer Lett. 2003;200:41–47
  20. Delie F, Rubas W. A human colonic cell line sharing similarities with enterocytes as a model to examine oral absorption: advantages and limitations of the Caco-2 model. Crit. Rev. Ther. Drug Carrier Syst. 1997;14:221–286
  21. Fleet JC, Wang L, Vitek O, Craig BA, Edenberg HJ. Gene expression profiling of Caco-2 BBe cells suggests a role for specific signaling pathways during intestinal differentiation. Physiol. Genomics. 2003;13:57–68
  22. Souleimani A, Asselin C. Regulation of c-myc expression by sodium butyrate in the colon carcinoma cell line Caco-2. FEBS Lett. 1993;326:45–50
  23. Murota K, Shimizu S, Chujo H, Moon JH, Terao J. Efficiency of absorption and metabolic conversion of quercetin and its glucosides in human intestinal cell line Caco-2. Arch. Biochem. Biophys. 2000;384:391–397
  24. Wenzel U, Kuntz S, Brendel MD, Daniel H. Dietary flavone is a potent apoptosis inducer in human colon carcinoma cells. Cancer Res. 2000;60:3823–3831
  25. Llor X, Pons E, Roca A, Alvarez M, Mane J, Fernandez-Banares F, et al. The effects of fish oil, olive oil, oleic acid and linoleic acid on colorectal neoplastic processes. Clin. Nutr. 2003;22:71–79
  26. Dzierzewicz Z, Orchel A, Weglarz L, Latocha M, Wilczok T. Changes in the cellular behaviour of human colonic cell line Caco-2 in response to butyrate treatment. Acta Biochim. Pol. 2002;49:211–220
  27. Wachtershauser A, Akoglu B, Stein J. HMG-CoA reductase inhibitor mevastatin enhances the growth inhibitory effect of butyrate in the colorectal carcinoma cell line Caco-2. Carcinogenesis. 2001;22:1061–1067
  28. Boersma MG, van der Woude H, Bogaards J, Boeren S, Vervoort J, Cnubben NH, et al. Regioselectivity of phase II metabolism of luteolin and quercetin by UDP-glucuronosyl transferases. Chem. Res. Toxicol. 2002;15:662–670
  29. Tietz NW, Rinker AD, Shaw LM. International federation of clinical chemistry. IFCC methods for the measurement of catalytic concentration of enzymes. Part 5. IFCC method for alkaline phosphatase (orthophosphoric-monoester phosphohydrolase, alkaline optimum, EC 3.1.3.1). IFCC document stage 2, draft 1, 1983-03 with a view to an IFCC recommendation. Clin. Chim. Acta. 1983;135:339F–367F
  30. Masungi C, Borremans C, Willems B, Mensch J, van Dijck A, Augustijns P, et al. Usefulness of a novel Caco-2 cell perfusion system. I. In vitro prediction of the absorption potential of passively diffused compounds. J. Pharm. Sci. 2004;93:2507–2521
  31. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976;72:248–254
  32. van der Woude H, Boersma MG, Vervoort J, Rietjens IM. Identification of 14 quercetin phase II mono- and mixed conjugates and their formation by rat and human phase II in vitro model systems. Chem. Res. Toxicol. 2004;17:1520–1530
  33. Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen elderly study. Lancet. 1993;342:1007–1011
  34. Weldin J, Jack R, Dugaw K, Kapur RP. Quercetin, an over-the-counter supplement, causes neuroblastoma-like elevation of plasma homovanillic acid. Pediatr. Dev. Pathol. 2003;6:547–551
  35. Yu Z, Li W, Liu F. Inhibition of proliferation and induction of apoptosis by genistein in colon cancer HT-29 cells. Cancer Lett. 2004;215:159–166
  36. Kuntz S, Wenzel U, Daniel H. Comparative analysis of the effects of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines. Eur. J. Nutr. 1999;38:133–142
  37. Lee KW, Hur HJ, Lee HJ, Lee CY. Antiproliferative effects of dietary phenolic substances and hydrogen peroxide. J. Agric. Food Chem. 2005;53:1990–1995
  38. van Erk MJ, Roepman P, van der Lende TR, Stierum RH, Aarts JM, van Bladeren PJ, et al. Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur. J. Nutr. 2004;44:143–156
  39. Wenzel U, Herzog A, Kuntz S, Daniel H. Protein expression profiling identifies molecular targets of quercetin as a major dietary flavonoid in human colon cancer cells. Proteomics. 2004;4:2160–2174
  40. Goodman JE, Bowman ED, Chanock SJ, Alberg AJ, Harris CC. Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms and colon cancer risk. Carcinogenesis. 2004;25:2467–2472
  41. Murota K, Shimizu S, Miyamoto S, Izumi T, Obata A, Kikuchi M, et al. Unique uptake and transport of isoflavone aglycones by human intestinal caco-2 cells: comparison of isoflavonoids and flavonoids. J. Nutr. 2002;132:1956–1961
  42. Graefe EU, Wittig J, Mueller S, Riethling AK, Uehleke B, Drewelow B, et al. Pharmacokinetics and bioavailability of quercetin glycosides in humans. J. Clin. Pharmacol. 2001;41:492–499
  43. Qiu Y, Waters CE, Lewis AE, Langman MJ, Eggo MC. Oestrogen-induced apoptosis in colonocytes expressing oestrogen receptor beta. J. Endocrinol. 2002;174:369–377
  44. Campbell-Thompson M, Lynch IJ, Bhardwaj B. Expression of estrogen receptor (ER) subtypes and ERbeta isoforms in colon cancer. Cancer Res. 2001;61:632–640
  45. Chen AC, Donovan SM. Genistein at a concentration present in soy infant formula inhibits Caco-2 BBe cell proliferation by causing G2/M cell cycle arrest. J. Nutr. 2004;134:1303–1308
  46. Zava DT, Duwe G. Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro. Nutr. Cancer. 1997;27:31–40
  47. Maggiolini M, Bonofiglio D, Marsico S, Panno ML, Cenni B, Picard D, et al. 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
  48. Bjeldanes LF, Chang GW. Mutagenic activity of quercetin and related compounds. Science. 1977;197:577–578
  49. Seino Y, Nagao M, Yahagi T, Sugimura T, Yasuda T, Nishimura S. Identification of a mutagenic substance in a spice, sumac, as quercetin. Mutat. Res. 1978;58:225–229
  50. Deschner EE, Ruperto J, Wong G, Newmark HL. Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia. Carcinogenesis. 1991;12:1193–1196
  51. Pereira MA, Grubbs CJ, Barnes LH, Li H, Olson GR, Eto I, et al. Effects of the phytochemicals, curcumin and quercetin, upon azoxymethane-induced colon cancer and 7,12-dimethylbenz[a]anthracene-induced mammary cancer in rats. Carcinogenesis. 1996;17:1305–1311
  52. Pamukcu AM, Yalciner S, Hatcher JF, Bryan GT. Quercetin, a rat intestinal and bladder carcinogen present in bracken fern (Pteridium aquilinum). Cancer Res. 1980;40:3468–3472
  53. Yang K, Lamprecht SA, Liu Y, Shinozaki H, Fan K, Leung D, et al. Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon. Carcinogenesis. 2000;21:1655–1660

PII: S0304-3835(05)00663-4

doi: 10.1016/j.canlet.2005.07.007

Cancer Letters
Volume 238, Issue 2 , Pages 248-259 , 18 July 2006

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