Cancer Chemoprevention by Dietary Proanthocyanidins

  • Jo, Jeong-Youn (Department of Food Science and Technology, Cornell University) ;
  • Lee, Chang-Yong (Department of Food Science and Technology, Cornell University)
  • Published : 2007.08.31

Abstract

Proanthocyanidins (PACs), also named condensed tannins, are polymers of flavan-3-ols such as (+ )-(gallo)catechin and (-)-epi(gallo)catechin. A proper analysis of the PACs, with difficult challenges due to their complex structures, is crucial in studies of cancer chemoprevention. Cancer is a leading cause of mortality around the world. Many experimental studies have shown that dietary PACs are potential chemopreventive agents that block or suppress against multistage carcinogenesis in both in vitro and in vivo models. Cancer chemoprevention by dietary PACs has been shown effective through different mechanisms of action such as antioxidant, apoptosis-inducing, and enzyme inhibitory activities. Good sources of dietary PACs are nuts, fruits, beans, chocolate, fruit juice, red wine, and green tea. The chemopreventive potential of dietary PACs should be considered together with their bioavailability in humans. The safety issues regarding carcinogenesis and gastrointestinal disorder are also reviewed.

Keywords

References

  1. Hagerman AE. Condensed tannin structural chemistry. In: Tannin Chemistry. Available from: http://www.users.muohio.edu/hagermae. Accessed Nov. 17, 2006
  2. Porter LJ. Flavans and proanthocyanidins. pp. 23-55. In: The Flavonoids- Advances in Research since 1986. Harborne JB (ed). Chapman and Hall, London, UK (1994)
  3. Gu L, Kelm MA, Hammerstone JF, Beecher G, Holden J, Haytowitz D, Gebhardt S, Prior RL. Concentrations of proanthocyanidins in common foods and estimations of normal consumption. J. Nutr. 134: 613-617 (2004)
  4. De Bruyne T, Pieters L, Deelstra H, Vlietinck A. Condensed vegetable tannins: Biodiversity in structure and biological activities. Biochem. Syst. Ecol. 27: 445-459 (1999) https://doi.org/10.1016/S0305-1978(98)00101-X
  5. Santos-Buelga C, Scalbert A. Proanthocyanidins and tannin-like compounds - nature, occurrence, dietary intake, and effects on nutrition and health. J. Sci. Food Agr. 80: 1094-1117 (2000) https://doi.org/10.1002/(SICI)1097-0010(20000515)80:7<1094::AID-JSFA569>3.0.CO;2-1
  6. Guyot S, Marnet N, Laraba, D, Sanoner P, Drilleau J-F. Reversedphase HPLC following thiolysis for quantitative estimation and characterization of the four main classes of phenolic compounds in different tissue zones of a French cider apple variety (Malus domestica var. Kermerrien). J. Agr. Food Chem. 46: 1698-1705 (1998) https://doi.org/10.1021/jf970832p
  7. Zhao J, Wang J, Chen Y, Agarwal R. Anti-tumor-promoting activity of a polyphenolic fraction isolated from grape seeds in the mouse skin two-stage initiation–promotion protocol and identification of procyanidin B5-3'-gallate as the most effective antioxidant constituent. Carcinogenesis 20: 1737-1745 (1999) https://doi.org/10.1093/carcin/20.9.1737
  8. Waterhouse AL, Price SF, McCord JD. Reversed-phase highperformance liquid chromatography methods for analysis of wine polyphenols. Method Enzymol. 29: 113-121 (1999)
  9. Kandil FE, Song L, Pezzuto M, Marley K, Seigler DS, Smith MAL. Isolation of oligomeric proanthocyanidins from flavonoid-producing cell cultures. In Vitro Cell. Dev. -Pl. 36: 492-500 (2000) https://doi.org/10.1007/s11627-000-0088-1
  10. Prieur C, Rigaud J, Cheynier V, Moutounet M. Oligomeric and polymeric procyanidins from grape seeds. Phytochemistry 36: 781- 784 (1994) https://doi.org/10.1016/S0031-9422(00)89817-9
  11. Kandil FE, Smith MAL, Rogers RB, Pépin MF, Song L, Pezzuto JM, Seigler D. Composition of a chemopreventive proanthocyanidinrich fraction from cranberry fruits responsible for the inhibition of 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity. J. Agr. Food Chem. 50: 1063-1069 (2002) https://doi.org/10.1021/jf011136z
  12. Jo JY, Gonzalez de Mejia E, Lila MA. Effects of grape cell culture extracts on human topoisomerase II catalytic activity and characterization of active fractions. J. Agr. Food Chem. 53: 2489- 2498 (2005) https://doi.org/10.1021/jf048524w
  13. Jo JY, de Mejia EG, Lila MA. Cytotoxicity of bioactive polymeric fractions from grape cell culture on human hepatocellular carcinoma, murine leukemia, and non-cancerous PK15 kidney cells. Food Chem. Toxicol. 44: 1758-1767 (2006) https://doi.org/10.1016/j.fct.2006.05.014
  14. Flamini R. Mass spectrometry in grape and wine chemistry. Part I: polyphenols. Mass Spectrom. Rev. 22: 218-250 (2003) https://doi.org/10.1002/mas.10052
  15. Cheynier V, Doco T, Fulcrand H, Guyot S, Le Roux E, Souquet JM, Riguad J, Moutounet M. ESI-MS analysis of polyphenolic oligomers and polymers. Analusis 25: 32-37 (1997)
  16. Gabetta B, Fuzzati N, Griffini A, Lolla E, Pace R, Ruffilli T, Peterlongo F. Characterization of proanthocyanidins from grape seeds. Fitoterapia 71: 162-175 (2000) https://doi.org/10.1016/S0367-326X(99)00161-6
  17. Wu Q, Wang M, Simon JE. Determination of proanthocyanidins in grape products by liquid chromatography/mass spectrometric detection under low collision energy. Anal. Chem. 75: 2440-2444 (2003) https://doi.org/10.1021/ac0262311
  18. Yousef GG, Seigler DS, Grusak MA, Rogers RB, Knight, CTG, Kraft TFB, Erdman Jr JW, Lila MA. Biosynthesis and characterization of $^{14}C$-enriched flavonoid fractions from plant cell suspension cultures. J. Agr. Food Chem. 52: 1138-1145 (2004) https://doi.org/10.1021/jf035371o
  19. World Health Organization. News releases 2006. Available from: http://www.who.int/mediacentre/news/releases/2006/en. Accessed Dec. 11, 2006
  20. Korea National Statistical Office. Cause of Death Statistics 2006. Available from: http://www.nso.go.kr. Accessed Dec. 11, 2006
  21. American Cancer Society. Cancer Statistics 2006. Available from: http://www.cancer.org. Accessed Dec. 11, 2006
  22. World Health Organization. Mortality Country Fact Sheet 2006. Available from: http://www.who.int/whosis/mort/profiles/en. Accessed Dec. 11, 2006
  23. Surh YJ. Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. Mutat. Res. 428: 305-327 (1999) https://doi.org/10.1016/S1383-5742(99)00057-5
  24. Hsu S, Yu FX, Huang Q, Lewis J, Singh B, Dickinson D, Borke J, Sharawy M, Wataha J, Yamamoto T, Osaki T, Schuster G. A mechanism-based in vitro anticancer drug screening approach for phenolic phytochemicals. Assay Drug Dev. Techn. 1: 611-618 (2003) https://doi.org/10.1089/154065803770380968
  25. Baek SJ, Kim JS, Jackson FR, Eling TE, McEntee MF, Lee SH. Epicatechin gallate-induced expression of NAG-1 is associated with growth inhibition and apoptosis in colon cancer cells. Carcinogenesis 25: 2425-2432 (2004) https://doi.org/10.1093/carcin/bgh255
  26. Babich H, Krupka ME, Nissim HA, Zuckerbraun HL. Differential in vitro cytotoxicity of (-)-epicatechin gallate (ECG) to cancer and normal cells from the human oral cavity. Toxicol. In Vitro 19: 231- 242 (2005) https://doi.org/10.1016/j.tiv.2004.09.001
  27. Kashiwada Y, Nonaka G, Nishioka I, Chang JJ, Lee KH. Antitumor agents. 129. Tannins and related compounds as selective cytotoxic agents. J. Nat. Prod. 55: 1033-1043 (1992) https://doi.org/10.1021/np50086a002
  28. Sakagami H, Kuribayashi N, Iida M, Sakagami T, Takeda M, Fukuchi K, Gomi K, Ohata H, Momose K, Kawazoe Y, Hatano T, Yoshida T, Okuda T. Induction of DNA fragmentation by tanninand lignin-related substances. Anticancer Res. 15: 2121-2128 (1995)
  29. Kolodziej H, Haberland C, Woerdenbag HJ, Konings AWT. Moderate cytotoxicity of proanthocyanidins to human tumour cell lines. Phytother. Res. 9: 410-415 (1995) https://doi.org/10.1002/ptr.2650090605
  30. Ye X, Krohn RL, Liu W, Joshi SS, Kuszynski CA, McGinn TR, Bagchi M, Preuss HG, Stohs SJ, Bagchi D. The cytotoxic effects of a novel IH636 grape seed proanthocyanidin extract on cultured human cancer cells. Mol. Cell Biochem. 196: 99-108 (1999) https://doi.org/10.1023/A:1006926414683
  31. Bagchi D, Sen CK, Ray SD, Das DK, Bagchi M, Preuss HG, Vinson JA. Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Mutat. Res. 523-524: 87-97 (2003)
  32. Bagchi D, Garg A, Krohn RL, Bagchi M, Bagchi DJ, Balmoori J, Stohs SJ. Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice. Gen. Pharmacol. 30: 771-776 (1998) https://doi.org/10.1016/S0306-3623(97)00332-7
  33. Bomser JA, Singletary KW, Wallig MA, Smith MA. Inhibition of TPA-induced tumor promotion in CD-1 mouse epidermis by a polyphenolic fraction from grape seeds. Cancer Lett. 135: 151-157 (1999) https://doi.org/10.1016/S0304-3835(98)00289-4
  34. Singletary KW, Meline B. Effect of grape seed proanthocyanidins on colon aberrant crypts and breast tumors in a rat dual-organ tumor model. Nutr. Cancer 39: 252-258 (2001) https://doi.org/10.1207/S15327914nc392_15
  35. Kim H, Hall P, Smith M, Kirk M, Prasain JK, Barnes S, Grubbs C. Chemoprevention by grape seed extract and genistein in carcinogeninduced mammary cancer in rats is diet dependent. J. Nutr. 134: 3445S-3452S (2004)
  36. Bagchi D, Bagchi M, Stohs S, Ray SD, Sen CK, Preuss HG. Cellular protection with proanthocyanidins derived from grape seeds. Ann. NY Acad. Sci. 957: 260-270 (2002) https://doi.org/10.1111/j.1749-6632.2002.tb02922.x
  37. Rahman A, Shahabuddin, Hadi SM, Parish JH, Ainley K. Strand scission in DNA induced by quercetin and Cu(II): role of Cu(I) and oxygen free radicals. Carcinogenesis 10: 1833-1839 (1989) https://doi.org/10.1093/carcin/10.10.1833
  38. Furukawa A, Oikawa S, Murata M, Hiraku Y, Kawanishi S. (-)- Epigallocatechin gallate causes oxidative damage to isolated and cellular DNA. Biochem. Pharmacol. 66: 1769-1778 (2003) https://doi.org/10.1016/S0006-2952(03)00541-0
  39. Yang CS, Hong J, Hou Z, Sang S. Green tea polyphenols: Antioxidative and prooxidative effects. J. Nutr. 134: 3181S (2004)
  40. Shao ZH, Hsu CW, Chang WT, Waypa GB, Li J, Li D, Li CQ, Anderson T, Qin Y, Schumacker PT, Becker LB, Hoek TL. Cytotoxicity induced by grape seed proanthocyanidins: role of nitric oxide. Cell Biol. Toxicol. 22: 149-158 (2006) https://doi.org/10.1007/s10565-006-0052-x
  41. Yang GY, Liao J, Kim K, Yurkow EJ, Yang CS. Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis 19: 611-616 (1998) https://doi.org/10.1093/carcin/19.4.611
  42. Chen C, Yu R, Owuor ED, Kong AN. Activation of antioxidantresponse element (ARE), mitogen-activated protein kinases (MAPKs), and caspases by major green tea polyphenol components during cell survival and death. Arch. Pharm. Res. 23: 605-612 (2000) https://doi.org/10.1007/BF02975249
  43. Lin JK. Cancer chemoprevention by tea polyphenols through modulating signal transduction pathways. Arch. Pharm. Res. 25: 561-571 (2002) https://doi.org/10.1007/BF02976924
  44. Gupta S, Hussain T, Mukhtar H. Molecular pathway for (-)- epigallocatechin-3-gallate-induced cell cycle arrest and apoptosis of human prostate carcinoma cells. Arch. Biochem. Biophys. 410: 177-185 (2003) https://doi.org/10.1016/S0003-9861(02)00668-9
  45. Berger SJ, Gupta S, Belfi CA, Gosky DM, Mukhtar H. Green tea constituent (-)-epigallocatechin-3-gallate inhibits topoisomerase I activity in human colon carcinoma cells. Biochem. Bioph. Res. Co. 288: 101-105 (2001) https://doi.org/10.1006/bbrc.2001.5736
  46. Boutwell RK. Diet and anticarcinogenesis in the mouse skin twostage model. Cancer Res. 43: 2465S-2468S (1983)
  47. Heck MM, Earnshaw WC. Topoisomerase II: A specific marker for cell proliferation. J. Cell Biol. 103: 2569-2581 (1986) https://doi.org/10.1083/jcb.103.6.2569
  48. Berger SJ, Tsai ML, Chatterjee S, Markowitz SD, Willson JKV, Berger NA. Transcriptional down regulation of topoisomerase II relative to topoisomerase I in normal and malignant human colon tissues; implications for therapy of colon cancer. P. Am. Assoc. Canc. Res. 34: 328 (1993)
  49. Chen MJ, Liang T, Zhou KY. Effect of proanthocyanidins on COX-2 enzyme activity and COX-2 mRNA/protein expression in LPSinduced RAW264.7 cells. Yao Xue Xue Bao 40: 406-409 (2005)
  50. Zhang WY, Liu HQ, Xie KQ, Yin LL, Li Y, Kwik-Uribe CL, Zhu XZ. Procyanidin dimer B2 [epicatechin-(4$\beta$-8)-epicatechin] suppresses the expression of cyclooxygenase-2 in endotoxin-treated monocytic cells. Biochem. Bioph. Res. Co. 345: 508-515 (2006) https://doi.org/10.1016/j.bbrc.2006.04.085
  51. Fang MZ, Wang Y, Ai N, Hou Z, Sun Y, Lu H, Welsh W, Yang CS. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res. 63: 7563-7570 (2003)
  52. Lee KW, Lee HJ. The roles of polyphenols in cancer chemoprevention. Biofactors 26: 105-121 (2006) https://doi.org/10.1002/biof.5520260202
  53. The US Department of Agriculture- Agricultural Research Service (USDA-ARS). USDA Database for the proanthocyanidin content of selected foods-2004. Available from: http://www.nal.usda.gov/fnic/ foodcomp/Data/PA/PA.html. Accessed Nov. 17, 2006
  54. Beecher GR. Proanthocyanidins: Biological activities associated with human health. Pharm. Biol. 42: 2S-20S (2004) https://doi.org/10.3109/13880200490893474
  55. Deprez S, Mila I, Huneau JF, Tome D, Scalbert A. Transport of proanthocyanidin dimer, trimer, and polymer across monolayers of human intestinal epithelial Caco-2 cells. Antioxid. Redox Sign. 3: 957-967 (2001) https://doi.org/10.1089/152308601317203503
  56. Deprez S, Brezillon C, Rabot S, Philippe C, Mila I, Lapierre C, Scalbert A. Polymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular-weight phenolic acids. J. Nutr. 130: 2733-2738 (2000)
  57. Scalbert A, Deprez S, Mila I, Albrecht AM, Huneau JF, Rabot S. Proanthocyanidins and human health: systemic effects and local effects in the gut. Biofactors 13: 115-120 (2000) https://doi.org/10.1002/biof.5520130119
  58. Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. Polyphenols: Food sources and bioavailability. Am. J. Clin. Nutr. 79: 727-747 (2004) https://doi.org/10.1093/ajcn/79.5.727
  59. Holt RR, Lazarus SA, Sullards MC, Zhu QY, Schramm DD, Hammerstone JF, Fraga CG, Schmitz HH, Keen CL. Procyanidin dimer B2 [epicatechin-(4$\beta$-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa. Am. J. Clin. Nutr. 76: 798-804 (2002) https://doi.org/10.1093/ajcn/76.4.798
  60. Ward NC, Croft KD, Puddey IB, Hodgson JM. Supplementation with grape seed polyphenols results in increased urinary excretion of 3-hydroxyphenylpropionic acid, an important metabolite of proanthocyanidins in humans. J. Agr. Food Chem. 52: 5545-5559 (2004) https://doi.org/10.1021/jf049404r
  61. Yang CS, Lee MJ, Chen L, Yang GY. Polyphenols as inhibitors of carcinogenesis. Environ. Health Perspect. 105: 971S-976S (1997) https://doi.org/10.2307/3433312
  62. Landau JM, Lambert JD, Lee MJ, Yang CS. Cancer prevention by tea and tea constituents. pp. 219-237. In: Carcinogenic and Anticarcinogenic Food Components. Baer-Dubowska W, Bartoszek A, Malejka-Giganti D (eds). CRC Press, Boca Raton, FL, USA (2006)
  63. Gao YT, McLaughlin JK, Blot WJ, Ji BT, Dai Q, Fraumeni JF Jr. Reduced risk of esophageal cancer associated with green tea consumption. J. Natl. Cancer I. 86: 855-858 (1994) https://doi.org/10.1093/jnci/86.11.855
  64. Zhong L, Goldberg MS, Gao YT, Hanley JA, Parent ME, Jin F. A population-based case-control study of lung cancer and green tea consumption among women living in Shanghai, China. Epidemiology 12: 695-700 (2001) https://doi.org/10.1097/00001648-200111000-00019
  65. Reed JD. Nutritional toxicology of tannins and related polyphenols in forage legumes. J. Anim. Sci. 73: 1516-1528 (1995)
  66. Dixon RA, Sumner LW. Legume natural products: understanding and manipulating complex pathways for human and animal health. Plant Physiol. 131: 878-885 (2003) https://doi.org/10.1104/pp.102.017319
  67. Awika JM, Rooney LW. Sorghum phytochemicals and their potential impact on human health. Phytochemistry 65: 1199-1221 (2004) https://doi.org/10.1016/j.phytochem.2004.04.001