Успехи молекулярной онкологии

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Механизмы антиканцерогенного действия флавоноидов

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Целью представленного обзора является анализ механизмов антиканцерогенного действия флавоноидов и изоцианатов на примере ряда соединений, широко употребляемых в средней полосе. В обзоре приведены данные исследований антиканцерогенного действия этих соединений в экспериментах in vitro и in vivo, рассмотрены мишени ингибирования действия химических канцерогенов в цепи их метаболизма, антиоксидантные эффекты флавоноидов, влияние пищевых полифенолов на метаболизм канцерогенных соединений, процессы промоции канцерогенеза и прогрессии опухоли, регуляцию клеточного цикла, цитоскелет и подвижность 
трансформированных клеток, индукцию апоптоза и неоангиогенез.

Об авторах

Г. А. Белицкий
ФГБУ «РОНЦ им. Н. Н. Блохина» РАМН, Москва

К. И. Кирсанов
ФГБУ «РОНЦ им. Н. Н. Блохина» РАМН, Москва

Е. А. Лесовая
ФГБУ «РОНЦ им. Н. Н. Блохина» РАМН, Москва

М. Г. Якубовская
ФГБУ «РОНЦ им. Н. Н. Блохина» РАМН, Москва

Список литературы

1. World Cancer Research Fund / American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of cancer: a Global Perspective. AICR, Washington, DC, 2007.

2. Panico S., Mattiello A., Panico C. et al. Mediterranean dietary pattern and chronic diseases. Cancer Treat Res 2014;159:69–81.

3. Riboli E., Norat T. Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am J Clin Nutr 2003;78:559–69.

4. Gonzalez C.A., Riboli E. Diet and cancer prevention: Contributions from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Eur J Cancer 2010;46:2555–62.

5. Buckland G., Agudo A., Lujan L. et al. Adherence to a Mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study. Am J Clin Nutr 2010;91:381–90.

6. Lam T.K., Gallicchio L., Lindsley K. et al. Cruciferous vegetable consumption and lung cancer risk: a systematic review. Cancer Epidemiol Biomarkers Prev 2009;18:184–95.

7. Gonzalez C.A., Lujan-Barroso L., Bueno- de-Mesquita H.B. et al. Fruit and vegetable intake nd the risk of gastric adenocarcinoma: a reanalysis of the European Prospective Investigation into ancer and Nutrition (EPIC-EURGAST) study after a longer follow-up. Int J ancer 2012;131(12):2910–9.

8. Grosso G., Buscemi S., Galvano F. et al. Mediterranean diet and cancer: epidemiological evidence and mechanism of selected aspects. BMC Surg 2013; 13(Suppl 2):S14.

9. Reszka E., Wasowicz W., Gromadzinska J. Genetic polymorphism of xenobiotic metabolizing enzymes, diet and cancer susceptibility. Br J Nutr 2006;96:609–19.

10. Hecht S.S. Inhibition of carcinogenesis by isothiocyanates. Drug Metab Rev 2000;32:395–411.

11. Lampe J.W. Diet, genetic polymorphisms, detoxification, and health risks. Altern Ther Health Med 2007;13:108–11.

12. Moon Y.J., Wang X., Morris M.E. Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro 2006;20(2):187–210.

13. So F.V., Guthrie N., Chambers A.F. et al. Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutr Cancer 1996;26:167–81.

14. Guthrie N., Carroll K.K. Inhibition of mammary cancer bycitrus flavonoids. Adv Exp Med Biol 1998;439: 227–36.

15. Constantinou A.I., Mehta R.G., Vaughan A. Inhibition of N-methyl-Nnitrosourea- induced mammary tumors in rats by the soybean isoflavones. Anticancer Res 1996;16:3293–8.

16. Lamartiniere C.A., Zhang J.X., Cotroneo M.S. Genisteinstudies in rats: potential for breast cancer prevention and eproductive and developmental toxicity. Am J Clin Nutr 1998;68:1400–5.

17. Hsieh C.Y., Santell R.C., Haslam S.Z. et al. Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res 1998;58:3833–8.

18. Wei H.C., Bowen R., Zhang X.S. et al. Isoflavonegenistein inhibits the initiation and promotion of two-stage skin carcinogenesisin mice. Carcinogenesis 1998;19:1509–14.

19. Tanaka T., Makita H., Ohnishi M. et al. Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis in rats by flavonoids diosmin and hesperidin, each alone and in combination. Cancer Res 1997;57:246–52.

20. Nixon J.E., Hendricks J.D., Pawlowski N.E. et al. Inhibition of aflatoxin B1 carcinogenesis in rainbow trout by flavone and indole compounds. Carcinogenesis 1984;5:615–9.

21. Devadoss D., Ramar M., Chinnasamy A. alangin, a dietary flavonol inhibits tumor initiation during experimental pulmonary tumorigenesis by modulating xenobiotic enzymes and antioxidant status. Arch Pharm Res 2014;doi: 10.1007/s12272-014-0330-8.

22. Deschner E.E., Rupert, J., Wong G. et al. Quercetinand rutin as inhibitors of azoxymethanol-induced colonic neoplasia. Carcinogenesis 1991;12:1193–6.

23. Tanaka T., Makita H., Kawabata K. et al. Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin. Carcinogenesis 1997;18:957–65.

24. Thiagarajan D.G., Bennink M.R., Bourquin L.D. et al. Prevention of precancerous colonic lesions in rats by soy flakes, soy flour, genistein, and calcium. Am J Clin Nutr 1998;68:1394–9.

25. Saud S.M., Young M.R., Jones-Hall Y.L. et al. Chemopreventive activity of plant flavonoid isorhamnetin in colorectal cancer is mediated by oncogenic Src and β-catenin. Cancer Res 2013;73(17):5473–84.

26. Lai C.S., Li S., Liu C.B. et al. Effective suppression of azoxymethane-induced aberrant crypt foci formation in mice with citrus peel flavonoids. Mol Nutr Food Res 2013:57(3):551–5.

27. Tsugane S., Sasazuki S. Diet and the risk of gastric cancer: review of epidemiological evidence. Gastric Cancer 2007;10:75–83.

28. Park B., Shin A., Park S.K. Ecological study for refrigerator use, salt, vegetable, and fruit intakes, and gastric cancer. Cancer Causes Control 2011;22:1497–502.

29. D’Elia L., Rossi G., Ippolito R. et al. Habitual salt intake and risk of gastric cancer: A metaanalysis of prospective studies. Clin Nutr 2012;31(4):489–98.

30. Tsugane S., Sasazuki S., Kobayashi M. et al. Salt and salted food intake and subsequent risk of gastric cancer amongmiddle-aged Japanese men and women. Br J Cancer 2004;90:128–34.

31. Lindsey S., Papoutsakis E.T. The evolving role of the aryl hydrocarbon receptor (AHR) in the normophysiology of hematopoiesis. Stem Cell Rev 2012;8(4):1223–35.

32. Кольман Я., Рем К. Г., Вирт Ю. Наглядная биохимия. М.: Мир, 2000; с. 302.

33. Walsh A.A., Szklarz G.D., Scott E.E. Human cytochrome P450 1A1 structure and utility in understanding drug and xenobiotic metabolism. J Biol Chem 2013;288(18):12932–43.

34. Wang B., Zhou S.F. Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem 2009;16(31):4066–218.

35. Lam T.K., Rotunno M., Lubin J.H. et al. Dietary quercetin, quercetin-gene interaction, metabolic gene expression in lung tissue, and lung cancer risk. Carcinogenesis 2010;31(4):634–42.

36. Poon C.H., Wong T.Y., Wang Y. et al. The citrus flavanone naringenin suppresses CYP1B1 transactivation through antagonising xenobiotic-responsive element binding. Br J Nutr 2013;109(9):1598–605.

37. Aranganathan S., Selvam J.P., Sangeetha N. et al. Modulatory efficacy of hesperetin (citrus flavanone) on xenobiotic-metabolizing enzymes during 1,2- imethylhydrazineinduced colon carcinogenesis. Chem Biol Interact 2009;180(2):254–61.

38. Vanhees K., van Schooten F.J., Moonen E.J. et al. Maternal intake of quercetin during gestation alters ex vivo benzo[a]pyrene metabolism and DNA adduct formation in adult offspring. Mutagenesis 2012;27(4): 445–51.

39. Makaji E., Ho S.H., Holloway A.C. et al. Effects in rats of maternal exposure to raspberry leaf and its constituents on the activity of cytochrome p450 enzymes in the offspring. Int J Toxicol 2011;30:216–24.

40. Vanhees K., Coort S., Ruijters E.J. et al. Epigenetics: prenatal exposure to genistein leaves a permanent signature on the hematopoietic lineage. FASEB J 2011;25:797–807.

41. Dolinoy D.C., Weidman J.R., Waterland R.A. et al. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ Health Perspect 2006;114:567–72.

42. de Figueiredo S.M., Filho S.A., Nogueira-Machado J.A. et al. The antioxidant properties of isothiocyanates: a review. Recent Pat Endocr Metab Immune Drug Discov 2013;7(3):213–25.

43. Heim K.E., Tagliaferro A.R., Bobilya D.J. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem 2002;13(10):572–84.

44. Singh B., Bhat N.K., Bhat H.K. Induction of NAD(P)H-quinone oxidoreductase 1 by antioxidants in female ACI rats is associated with decrease in oxidative DNA damage and inhibition of estrogen-induced breast cancer. Carcinogenesis 2012;33(1):156–63.

45. Hu R., Xu C., Shen G. et al. Identification of Nrf2-regulated genes induced by chemopreventive isothiocyanate PEITC by oligonucleotide microarray. Life Sci 2006; 79(20):1944–55.

46. Yang C.S., Wang X., Lu G. et al. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer 2009;9(6):429–39.

47. Vondracek J., Umannova L., Machala M. Interactions of the aryl hydrocarbon receptor with inflammatory mediators: beyond CYP1A regulation. Drug Metab 2011;12(2):89–103.

48. During A., Larondelle Y. The O-methylation of chrysin markedly improves its intestinal anti-inflammatory properties: Structure-activity relationships of flavones. Biochem Pharmacol 2013;86(12):1739–46.

49. Luqman S., Pezzuto J.M. NFkappaB: a promising target for natural products in cancer chemoprevention. Phytother Res 2010;24:949–63.

50. Ahmad N., Gupta S., Mukhtar H. Green tea polyphenol epigallocatechin-3-gallate differentially modulates nuclear factor κB in cancer cells versus normal cells. Arch Biochem Biophys 2000;376:338–46.

51. Wheeler D.S., Catravas J.D., Odoms K. et al. Epigallocatechin-3-gallate, a green tea-erived polyphenol, inhibits IL-1 betadependent proinflammatory signal transduction in cultured respiratory epithelial cells. J Nutr 2004;134(5):1039–44.

52. Vanhees K., van Schooten F.J., v an Waalwijk van Doorn-Khosrovani S.B. et al. Intrauterine exposure to flavonoids modifies antioxidant status at adulthood and decreases oxidative stress-induced DNA damage. Free Radic Biol Med 2013;57: 154–61.

53. Bonacasa B., Siow R.C., Mann G.E. Impact of dietary soy isoflavones in pregnancy on fetal programming of endothelial function in offspring. Microcirculation 2011;18:270–85.

54. Boots A.W., Drent M., de Boer V.C. et al. Quercetin reduces markers of oxidative stress and inflammation in sarcoidosis. Clin Nutr 2011;30:506–12.

55. Barhoover M.A., Hall J.M., Greenlee W.F. et al. Aryl hydrocarbon receptor regulates cell cycle progression in human breast cancer cells via a functional interaction with yclindependent kinase 4. Mol. Pharmacol 2010;77(2):195–201.

56. Lee K.W., Kang N.J., Heo Y.S. et al. Raf and MEK protein kinases are direct molecular targets for the chemopreventive effect of quercetin, a major flavonol in red wine. Cancer Res 2008;68:946–55.

57. Wang C., Xu C.X., Bu Y. et al. Beta-naphthoflavone (DB06732) mediates estrogen receptor-positive breast cancer cell cycle arrest through AhR-dependent regulation of PI3K/AKT and MAPK/ERK signaling. Carcinogenesis 2014;35(3):703–13.

58. Ermakova S., Choi B.Y., Choi H.S. et al. The intermediate filament protein vimentin is a new target for epigallocatechin gallate. J Biol Chem 2005;280:16882–90.

59. Ermakova S.P., Kang B.S., Choi B.Y. et al. (-)-Epigallocatechin gallate overcomes resistance to etoposide-induced cell death by targeting the molecular chaperone lucoseregulated protein 78. Cancer Res 2006;66:9260–9.

60. Deng Y.T., Lin J.K. EGCG inhibits the invasion of highly invasive CL1-5 lung cancer cells through suppressing MMP-2 expression via JNK signaling and induces G2/M arrest. J Agric Food Chem 2011;59(24):13318–27.

61. Roomi M.W., Monterrey J.C., Kalinovsky T. et al. Comparative effects of EGCG, green tea and a nutrient mixture on the patterns of MMP-2 and MMP-9 expression in cancer cell lines. Oncol Rep 2010;24(3):747–57.

62. Garbisa S., Sartor L., Biggin S. et al. Tumor gelatinases and invasion inhibited by the green tea flavanol epigallocatechin-3-gallate. Cancer 2001;91:822–32.

63. Jankun J., Selman S.H., Swiercz R. et al. Why drinking green tea could prevent cancer. Nature 1997;387(6633):561.

64. Slivova V., Zaloga G., DeMichele S.J. et al. Green tea polyphenols modulate secretion of urokinase plasminogen activator (uPA) and inhibit invasive behavior of breast cancer cells. Nutr Cancer 2005;52(1):66–73.

65. Zhang X., Min K.W., Wimalasena J. et al. Cyclin D1 degradation and p21 induction contribute to growth inhibition of colorectal cancer cells induced by epigallocatechin-3-gallate. J Cancer Res Clin Oncol 2012;138(12):2051–60.

66. Parajuli B., Shin S.J., Kwon S.H. et al. The synergistic apoptotic interaction of Indole-3-Carbinol and Genistein with TRAIL on endometrial cancer cells. J Korean Med Sci 2013;28(4):527–33.

67. Bertolini F., Fusetti L., Rabascio C. et al. Inhibition of angiogenesis and induction of endothelial and tumor cell apoptosis by green tea in animal models of human high-grade non-Hodgkin's lymphoma. Leukemia 2000;14:1477–82.

68. Tang F.Y., Nguyen N., Meydani M. Green tea catechins inhibit VEGF-induced angiogenesis in vitro through suppression of VE-cadherin phosphorylation and inactivation of Akt molecule. Int J Cancer 2003;106(6):871–8.

69. Sagara Y., Miyata Y., Nomata K. et al. Green tea polyphenol suppresses tumor invasion and angiogenesis in N-butyl-(-4-hydroxybutyl) nitrosamine-induced bladder cancer. Cancer Epidemiol 2010;34(3):350–4.

70. Ohga N., Hida K., Hida Y. et al. Inhibitory effects of epigallocatechin-3 gallate, a polyphenol in green tea, on tumorassociated endothelial cells and endothelial progenitor cells. Cancer Sci 2009;100(10):1963–70.

71. Leong H., Mathur P.S., Greene G.L. Green tea catechins inhibit angiogenesis through suppression of STAT3 activation. Breast Cancer Res Treat 2009; 117(3):505–15.

72. Shin J.H., Zhang L., Murillo-Sauca O. et al. Modulation of natural killer cell antitumor activity by the aryl hydrocarbon receptor. Proc Natl Acad Sci USA 2013;110(30):12391–6.

73. Uckun F.M., Narla R.K., Zeren T. et al. In vivo toxicity, pharmacokinetics, and anticancer activity of Genistein linked to recombinant human epidermal growth factor. Clin Cancer Res 1998;4(5):1125–34.

74. Galati G., O'Brien P.J. Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Radic Biol Med 2004;37(3):287–303.

75. Hirose M., Hoshiya T., Mizoguchi Y. et al. Green tea catechins enhance tumor development in the colon without effects in the lung or thyroid after pre-treatment with 1,2-dimethylhydrazine or 2,2V-dihydroxy-di- n-propylnitrosamine in male F344 rats. Cancer Lett 2001;168:23–9.

76. Skibola C. F., Smith M. T. Potential health impacts of excessive flavonoid intake. Free Radic Biol Med 2000;29:375–83.

77. Kyselova Z. Toxicological aspects of the use of phenolic compounds in disease prevention. Interdiscip Toxicol 2011;4(4):173–83.

78. Jia L., Liu F.T. Why bortezomib cannot go with 'green'? Cancer Biol Med 2013;10(4):206–13.

79. Nguyen M.A., Staubach P., Wolffram S. et al. Effect of single-dose and short-term administration of quercetin on the pharmacokinetics of talinolol in humans - Implications for the evaluation of transportermediated fаlavonoid-drug interactions. Eur J Pharm Sci 2014;61:54–60.

Для цитирования:

Белицкий Г.А., Кирсанов К.И., Лесовая Е.А., Якубовская М.Г. Механизмы антиканцерогенного действия флавоноидов. Успехи молекулярной онкологии. 2014;1(1):56-68.

For citation:

Belitsky G.A., Kirsanov K.I., Lesovaya E.A., Yakubovskaya M.G. Mechanisms of carcinogenesis prevention by flavonoids. Advances in molecular oncology. 2014;1(1):56-68. (In Russ.)

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