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Flavonoids and Gene Expression in Mammalian Cells

  • Shiu-Ming Kuo
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 505)

Abstract

Flavonoids are found to be widely present in the plant kingdom and possess diverse biological activities. The focus of this review is on their regulation of gene expression in mammalian cells. Although a direct DNA-flavonoid interaction could be demonstrated (Ahmed et al., 1994; Strick et al., 2000), this reaction lacks the DNA sequence specificity that is needed for gene regulation. Indeed, no particular gene regulation was reported as a consequence of the DNA-flavonoid interaction. Instead, flavonoids appear to regulate gene expression through interactions with protein transcription factors as described below. Most of the studies in this area examined dietary flavonoids. Some medicinal and synthetic flavonoid-like compounds have also been developed for potential pharmaceutical applications.

Keywords

Human Colon Cancer Cell Prostate Carcinoma Cell Quinone Reductase Human Intestinal Cell Metallothionein Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Ahmed, M. S., Ramesh, V., Nagaraja; V., Parish, J. H., and Hadi, S. M., 1994, Mode of binding of quercetin to DNA, Mutagenesis 9: 193–197.CrossRefGoogle Scholar
  2. Atluru, D., Jackson, T. M., and Atluru, S., 1991, Genistein, a selective protein tyrosine kinase inhibitor, inhibits interleukin-2 and leukotriene B4 production from human mononuclear cells, Clin. Immunol Immunopathol. 59: 379–387.CrossRefGoogle Scholar
  3. Bos, J. L., 1989, Ras oncogenes in human cancer: A review, Cancer Res. 49: 4682–4689.Google Scholar
  4. Brown, A., Jolly, P., and Wei, H., 1998, Genistein modulates neuroblastoma cell proliferation and differentiation through induction ofapoptosis and regulation of tyrosine kinase activity and N-myc expression, Carcinogenesis 19: 991–997.CrossRefGoogle Scholar
  5. Brown, N. M., Wang, J., Cotroneo, M. S., Zhao, Y. -X., and Lamartiniere, C. A., 1998, Prepubertal genistein treatment modulates TGF-a, EGF and EGF-receptor mRNAs and proteins in the rat mammary gland, Mol Cell. Endocrinol. 144: 149–165.CrossRefGoogle Scholar
  6. Cai, Q., and Wei, H., 1996, Effect of dietary genistein on antioxidant enzyme activities in SENCAR mice, Nutr. Cancer 25: 1–7.CrossRefGoogle Scholar
  7. Carlson, B., Lahusen, T., Singh, S., Loaiza-Perez. A., Worland, P. J., Pestell, R., Albanese, C., Sausville, E. A., and Senderowicz, A. M., 1999, Down-regulation ofCyclin DI by transcriptional repression in MCF-7 human breast carcinoma cells induced by flavopiridol, Cancer Res. 59: 4634–4641.Google Scholar
  8. Choi, Y. H., Lee, W. H., and Zhang, L., 2000, p53 independent induction of p2I (WAF 1 /CiP 1), reduction of cyclin B1 and G2/M arrest by the isoflavone genistein in human prostate carcinoma cells, Jpn. J. Cancer Res. 91: 164–171.CrossRefGoogle Scholar
  9. Chung, J. Y., Huang, C., Meng, X., Dong, Z., and Yang, C. S., 1999, Inhibition of activator protein 1 activity and cell growth by purified green tea and black tea polyphenols in H-ras-transformed cells: structure-activity relationship and mechanisms involved, Cancer Res. 59: 4610–4617.Google Scholar
  10. Dees, C., Foster, J. S., Ahamed, S., and Wimalasena, J., 1997, Dietary estrogens stimulate human breast cells to enter the cell cycle, Environ. Health Perspect. 105 (Suppl 3): 633–636.CrossRefGoogle Scholar
  11. Galvez, J., De La Cruz, J. P., Zarzuelo, A., De Medina, F. S. Jr., Jimenez, J., and De La Cuesta, F. S., 1994, Oral administration of quercitrin modifies intestinal oxidative status in rats, Gen. Pharmac. 25: 1237–1243.CrossRefGoogle Scholar
  12. Gerritsen, M. E., Carley, W. W., Ranges, G. E., Shen, C. -P., Phan, S. A., Ligon, G. F., and Perry, C. A., 1995, Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression, Am. J. Pathol. 147: 278–292.Google Scholar
  13. Helsby, N. A., Willaims, J., Kerr, D., Gescher, A., and Chipman, J. K., 1997, The isoflavones equol and genistein do not induce xenobiotic-metabolizing enzymes in mouse and in human cells, Xenobiotica 6: 587–596.CrossRefGoogle Scholar
  14. Hill, C. S., and Treisman, R., 1995, Transcriptional regulation by extracellular signals: mechanisms and specificity, Cell 80: 199–211.CrossRefGoogle Scholar
  15. Hosokawa, N., Hosokawa, Y., Sakai, T., Yoshida, M., Marui, N., Nishino, H., Kawai, K., and Aoike, A., 1990, Inhibitory effect of quercetin on the synthesis of a possibly cell-cycle-related 17-kDa protein, in human colon cancer cells, Int. J. Cancer 45: 1119–1124.CrossRefGoogle Scholar
  16. Hsieh, C. -Y., Santell, R. C., Haslam, S. Z., and Helferich, W. G., 1998, Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo, Cancer Res. 58: 3833–3838.Google Scholar
  17. Ishiwa, J., Sato, T., Mimaki, Y., Sashida, Y., Yano, M., and Ito, A., 2000, A citrus flavonoid, nobiletin, suppresses production and gene expression of matrix metalloproteinase 9/gelatinase B in rabbit synovial fibroblasts, J. Rheumatol. 27: 20–25.Google Scholar
  18. Kameoka, S., Leavitt, P. S., Chang, C., and Kuo, S. -M., 1999, Expression of antioxidant proteins in human intestinal Caco-2 cells treated with dietary flavonoids, Cancer Leu. 146: 161–167.CrossRefGoogle Scholar
  19. Kang, Z. C., Tsai, S. J., and Lee, H., 1999, Quercetin inhibits benzo[a]pyrene-induced DNA adducts in human Hep G2 cells by altering cytochrome P-450 lAl gene expression, Nutr. Cancer 35: 175–159.CrossRefGoogle Scholar
  20. Kawada, N., Seki, S., Inoue, M., and Kuroki, T., 1998, Effect of antioxidants, resveratrol, quercetin, and Nacetylcysteine, on the functions of cultured rat hepatic stellate cells and Kupffer cells, Hepatology 27: 1265–1274.CrossRefGoogle Scholar
  21. Kobuchi, H., Virgili, F., and Packer, L., 1999, Assay of inducible form of nitric oxide synthase activity: effect of flavonoids and plant extracts, Methods in Enzymol. 301: 504–513.CrossRefGoogle Scholar
  22. Krol, W., Czuba, Z. P., Threadgill, M. D., Cunningham, B. D., and Pietsz, G., 1995, Inhibtion of nitric oxide production in murine macrophages by flavones, Biochem. Pharmacol. 50: 1031–1035.CrossRefGoogle Scholar
  23. Kuiper, G., Lemmen, J., Carlsson, B., Corton, J.. Safe, S., van der Saag, P.. van der Burg, B., and Gustafsson, J.-A., 1998, Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor B, Endocrinology 139: 4252–4263.CrossRefGoogle Scholar
  24. Kuo, S.-M., 1996, Antiproliferative potency of structurally distinct dietary flavonoids on human colon cancer cells, Cancer Lett. 110: 41–48.CrossRefGoogle Scholar
  25. Kuo, S.-M., 1997, Dietary flavonoid and cancer prevention: evidence and potential mechanism, Critical Rev. Oncogenesis 8: 47–69.CrossRefGoogle Scholar
  26. Kuo, S. -M., 1998, Transepithelial transport and accumulation of flavone in human intestinal Caco-2 cells, Life Sci. 63: 2323–2331.CrossRefGoogle Scholar
  27. Kuo, S. -M., Leavitt, P. S., and Lin, C. -P., 1998, Dietary flavonoids interact with trace metals and affect metallothionein level in human intestinal cells, Biol. Trace Element Res. 62: 135–153.CrossRefGoogle Scholar
  28. Kuo, S. -M., and Leavitt, P. S., 1999, Genistein increases metallothionein expression in human intestinal cells, Caco-2, Biochem. Cell Biol. 77: 79–88.CrossRefGoogle Scholar
  29. Kuo, S. -M., Leavitt, P. S., and Chang, C.,1999, Cytokines and metallothionein expression in human intestinal Caco-2 cells, FASEBJ. 13: A1505.Google Scholar
  30. Kuo, S. -M., Huang, C.-T., Blum, P., and Chang, C., 2001, Quercetin cumulatively enhances copper induction of metallothionein in intestinal cells, Biol. Trace Element Res.. (in press).Google Scholar
  31. Kurzer, M., and Xu, X., 1997, Dietary phytoestrogens, Annu. Rev. Nutr. 17: 353–381.CrossRefGoogle Scholar
  32. Kuzumaki, T., Kobayashi, T., and Ishikawa, K.,1998, Genistein induces p21Cip1WAF1 expression and blocks the GI to S phase transition in mouse fibroblast and melanoma cells, Biochem. Biophys. Res. Comm. 251: 291–295.CrossRefGoogle Scholar
  33. Liang, Y. C., Huang, Y. T., Tsai, S. H., Lin-Shiau, S. Y., Chen, C. F., and Lin, J. K., 1999, Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages, Carcinogenesis 20: 1945–1952.CrossRefGoogle Scholar
  34. Mäkelä, S., Davis, V. L., Tally W. C., Korkman, J., Salo, L., Vihko, R., Santti, R., and Korach, K. S., 1994, Dietary estrogens act through estrogen receptor-mediated processes and show no antiestrogenicity in cultured breast cancer cells, Environ. Health Perspect. 102: 572–578.CrossRefGoogle Scholar
  35. Manthey, J. A., Grohmann, K., Montanari, A., Ash, K., and Manthey, C. L., 1999, Polymethoxylated flavones derived from citrus suppress tumor necrosis factor-alpha expression by human monocytes, J. Natural Products 62: 441–444.CrossRefGoogle Scholar
  36. Miksicek, R. J., 1993, Commonly occurring plant flavonoids have estrogenic activity, Mol. Pharmacol. 44: 37–43.Google Scholar
  37. Miksicek, R. J., 1994, Interaction of naturally occurring non-steroidal estrogens with the recombinant human estrogen receptor, J. Steroid Biochem. Mol. Biol. 49: 153–160.CrossRefGoogle Scholar
  38. Mutoh, M., Takahashi, M., Fukuda, K., Matsushima-Hibiya, Y., Mutoh, H., Sugimura, T., and Wakabayashi, K., 2000, Suppression of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells by chemopreventive agents with a resorcin-type structure, Carcinogenesis 21: 959–963.CrossRefGoogle Scholar
  39. Oberley, L. W., McCormick, M. L., Sierra-Rivera, E., and St. Clair, D. K., 1989, Manganese superoxide dismutase in normal and transformed human embryonic lung fibroblasts, Free Radical Biol. Med. 6: 379–384.CrossRefGoogle Scholar
  40. Ranelletti, F. O., Maggiano, N., Serra, F. G., Ricci, R., Larocca, L. M., Lanza, P., Scambia, G., Fattorossi, A., Capelli, A., and Piantelli, M., 2000, Quercetin inhibits p21-Ras expression in human colon cancer cell lines and in primary colorectal tumors, Int. J Cancer 85: 438–445.CrossRefGoogle Scholar
  41. Sanz, M. J., Ferrandiz, M. L., Cejudo, M., Terencio, M. C., Gil, B., Bustos, G., Ubeda, A., Gunasegaran, R., and Alcaraz, M. J., 1994, Influence of a series of natural flavonoids on free radical generating systems and oxidative stress, Xenobiotica 24: 689–699.CrossRefGoogle Scholar
  42. Sathyamoorthy, N., Wang, T. T. Y., and Phang, J. M., 1994. Stimulation of pS2 expression by diet-derived compounds, Cancer Res. 54: 957–961.Google Scholar
  43. Sathyamoorthy, N., Gilsdorf, J., and Wang, T., 1998, Differential effect ofgenistein on transforming growth factor 31 expression in normal and malignant mammary epithelial cells, Anticancer Res. 18: 2449–2454.Google Scholar
  44. Scambia, G., Panici, P. B., Ranelletti, F. O., Ferrandina, G., De Vincenzo, R., Piantelli, M., Masciullo, V., Bonanno, G., Isola, G., and Mancuso, S., 1994, Quercetin enhances transforming growth factor ßl secretion by human ovarian cancer cells, Int. J. Cancer 57: 211–215.CrossRefGoogle Scholar
  45. Segaert, S., Courtois, S., Garmyn, M., Degreef, H., and Bouillon, R., 2000, The flavonoid apigenin suppresses vitamin D receptor expression and vitamin D responsiveness in normal human keratinocytes, Biochem. Biophys. Res. Comm. 268: 237–241.CrossRefGoogle Scholar
  46. Shao, Z. -M., Wu, J., Shen, Z. -Z., and Barsky, S. H., 1998, Genistein exerts multiple suppressive effects on human breast carcinoma cells, Cancer Res. 58: 1851–1857.Google Scholar
  47. Sherr, C. J., 1993, Mammalian GI cyclins, Cell 73: 1059–1065.CrossRefGoogle Scholar
  48. Sherr, C. J., 1994, GI phase progression: cycling on cue, Cell 79: 551–555.CrossRefGoogle Scholar
  49. Song, L. L., Kosmederll, J. W., Lee, S. K., Gerhäuser, C., Lantvit, D., Moon, R. C., Moriarty, R. M., and Pezzuto, J. M., 1999, Cancer chemopreventive activity mediated by 4’-bromoflavone, a potent inducer of phase II detoxification enzymes, Cancer Res. 59: 578–585.Google Scholar
  50. Steele. V. E., Kellof, G. J., Balentine, D., Boone, C. W., Mehta, R.. Bagheri, D., Sigman, C. C., Zhu, S., and Sharma, S., 2000, Comparative chemopreventive mechanisms of green tea, black tea and selected polyphenol extracts measured by in vitro bioassays, Carcinogenesis 21: 63–67.Google Scholar
  51. Strick, R., Strissel, P. L., Borgers, S., Smith, S. L., and Rowley, J. D., 2000, Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia, Proc. Natl. Acad. Sci. 97: 4790–4795.CrossRefGoogle Scholar
  52. Tabary, O., Escotte, S., Couetil, J. P., Hubert, D., Dusser, D., Puchelle, E., and Jacquot. J., 1999, Genistein inhibits constitutive and inducible NFKß activation and decreases IL-8 production by human cystic fibrosis bronchial gland cells, Am. J Pathol. 155: 473–481.CrossRefGoogle Scholar
  53. Uchiyama, T., Kurabayashi, M., Ohyama, Y., Utsugi, T., Akuzawa, N., Sato, M., Tomono, S., Kawazu, S., and Nagai, R., 2000, Hypoxia induces transcription of the plasminogen activator inhibitor-I gene through genistein-sensitive tyrosine kinase pathways in vascular endothelial cells, Arterioscler. Thromb. Vasc. Biol. 20: 1155–1161.CrossRefGoogle Scholar
  54. Wadsworth, T. L., and Koop, D. R., 1999, Effects of the wine polyphenolic quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages, Biochem. Pharmacol. 57: 941–949.CrossRefGoogle Scholar
  55. Wang, Y., E, Y., Zhang, X., Lebwohl, M., DeLeo, V., and Wei, H., 1998, Inhibition of ultraviolet B- induced c-fos and c-jun expression in vivo by a tyrosine kinase inhibitor genistein, Carcinogenesis 19: 649–654.CrossRefGoogle Scholar
  56. Wei, H., Tye, L., Bresnick, E., and Bin, D. F., 1990, Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice, Cancer Res. 50: 499–502.Google Scholar
  57. Zi, X., and Agarwal, R., 1999, Silibinin decreases prostate-specific antigen with cell growth inhibition via GI arrest, leading to differentiation of prostate carcinoma cells: implications for prostate cancer intervention, Proc. Natl. Acad. Sci. 96: 7490–7495.CrossRefGoogle Scholar
  58. Zhao, J., Lahiri-Chatterjee, M.. Sharma, Y., and Agarwal, R., 2000, Inhibitory effect of a flavonoid antioxidant silymarin on benzoyl peroxide-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin, Carcinogenesis 21: 811–816.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Shiu-Ming Kuo
    • 1
  1. 1.Department of Physical Therapy, Exercise and Nutrition Sciences, Department of BiochemistryState University of New York at BuffaloBuffaloUSA

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