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Phytoestrogens as a Natural Source for the Possible Colon Cancer Treatment

  • Suresh Challa
  • Rajanna Ajumeera
  • Naresh Venna
Chapter

Abstract

Phytoestrogens (PEs) are naturally available bioactive compounds widely available in a spectrum of sources such as plant foods and are said to exhibit estrogen-like, antioxidant, and anticancer properties. There are wide range of PE-containing sources which are usually consumed by humans such as isoflavones (IF), coumestans, and lignans. Many of the fruits, vegetables, and whole grains are known to contain PE. For example, soybeans mainly contain IF, and flaxseeds mostly contain lignans, while clover, alfalfa, and soybean sprouts are rich in coumestans. There are many factors which affect the way these compounds act in a cell type such as estrogen receptor (ER)-α and ER-β levels and the amount of co-activators and corepressors present. The proposed mechanism by which these PEs work is by exerting their antioxidant effects through the inhibition of tyrosine kinase as well as DNA topoisomerase activities and also by suppressing the process of angiogenesis. Findings from molecular, cellular, and animal studies suggest that PE may potentially confer health benefits related to colon cancer (CC) pathology. High incidence of CC might be resulted with the intake of high-calorie diet including consumption of saturated fat and practicing sedentary lifestyle, whereas PEs from fiber-rich food could serve as prophylactics. The aim of this chapter is to elucidate the mechanistic approaches of different plant-based estrogens in combating colon cancer and their possible beneficial and clinical effects and therapeutic implications.

Keywords

Benefits Colon cancer Consumption Isoflavones Phytoestrogens 

References

  1. Akhter M, Inoue M, Kurahashi N, Iwasaki M, Sasazuki S, Tsugane S (2008) Dietary soy and isoflavone intake and risk of colorectal cancer in the japan public health center-based prospective study. Cancer Epidemiol Biomark Prev 17:2128–2135CrossRefGoogle Scholar
  2. Amawi H, Ashby CR, Tiwari AK (2017) Cancer chemoprevention through dietary flavonoids: what’s limiting. Chin J Cancer 36:50.  https://doi.org/10.1186/s40880-017-0217-4 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Anderson JJ, Anthony M, Messina M, Garne SC (1999) Effects of phyto-oestrogens on tissues. Nutr Res Rev 12:75–116CrossRefPubMedGoogle Scholar
  4. André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350:2343–2351CrossRefPubMedGoogle Scholar
  5. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F (2017) Global patterns and trends in colorectal cancer incidence and mortality. Gut 66:683–691CrossRefPubMedGoogle Scholar
  6. Bao B, Wang Z, Ali S, Kong D, Li Y, Ahmad A, Banerjee S, Azmi AS, Miele L, Sarkar FH (2011) Notch-1 induces epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells. Cancer Lett 307:26–36CrossRefPubMedPubMedCentralGoogle Scholar
  7. Barnes S (2010) The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products. Lymphat Res Biol 8:89–98CrossRefPubMedPubMedCentralGoogle Scholar
  8. Barone M, Tanzi S, Lofano K, Scavo MP, Guido R, Demarinis L, Principi MB, Bucci A, Di Leo A (2008) Estrogens, PE and colorectal neoproliferative lesions. Genes Nutr 3:7–13CrossRefPubMedPubMedCentralGoogle Scholar
  9. Bielenberg DR, Zetter BR (2015) The contribution of angiogenesis to the process of metastasis. Cancer J 21:267–273CrossRefPubMedPubMedCentralGoogle Scholar
  10. Birt DF, Hendrich S, Wang W (2001) Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacol Ther 90:157–177CrossRefPubMedGoogle Scholar
  11. Blanco A, Habib A, Levy-Toledano S, Maclouf J (1995) Involvement of tyrosine kinases in the induction of cyclo-oxygenase-2 in human endothelial cells. Biochem J 312:419–423CrossRefPubMedPubMedCentralGoogle Scholar
  12. Block G, Patterson B, Subar A (1992) Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr Cancer 18:1–29CrossRefPubMedGoogle Scholar
  13. Brownson DM, Azios NG, Fuqua BK, Dharmawardhane SF, Mabry TJ (2002) Flavonoid effects relevant to cancer. J Nutr 132:S3482–S3489CrossRefGoogle Scholar
  14. Budhathoki S, Joshi AM, Ohnaka K, Yin G, Toyomura K, Kono S, Mibu R, Tanaka M, Kakeji Y, Maehara Y (2011) Soy food and isoflavone intake and colorectal cancer risk: the fukuoka colorectal cancer study. Scand J Gastroenterol 46:165–172CrossRefPubMedGoogle Scholar
  15. Chen J, Stavro PM, Thompson LU (2002) Dietary flaxseed inhibits human breast cancer growth and metastasis and downregulates expression of insulin-like growth factor and epidermal growth factor receptor. Nutr Cancer 43:187–192CrossRefPubMedGoogle Scholar
  16. Ciombor KK, Wu C, Goldberg RM (2015) Recent therapeutic advances in the treatment of colorectal cancer. Annu Rev Med 66:83–95CrossRefPubMedGoogle Scholar
  17. Colussi D, Brandi G, Bazzoli F, Ricciardiello L (2013) Molecular pathways involved in colorectal cancer: implications for disease behavior and prevention. Int J Mol Sci 14:16365–16385CrossRefPubMedPubMedCentralGoogle Scholar
  18. Cotterchio M, Boucher BA, Manno M, Gallinger S, Okey A, Harper P (2006) Dietary phytoestrogen intake is associated with reduced colorectal cancer risk. J Nutr 136:3046–3053CrossRefPubMedPubMedCentralGoogle Scholar
  19. Crockett SD, Snover DC, Ahnen DJ, Baron JA (2015) Sessile serrated adenomas: an evidence-based guide to management. Clin Gastroenterol Hepatol 13:11–26CrossRefPubMedGoogle Scholar
  20. Dabrosin C, Chen J, Wang L, Thompson LU (2002) Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts. Cancer Lett 185:31–37CrossRefPubMedGoogle Scholar
  21. de Jong AE, Morreau H, Nagengast FM, Mathus-Vliegen EM, Kleibeuker JH, Griffioen G, Cats A, Vasen HF (2005) Prevalence of adenomas among young individuals at average risk for colorectal cancer. Am J Gastroenterol 100:139–143CrossRefPubMedGoogle Scholar
  22. Dixon RA (2004) Phytoestrogens. Annu Rev Plant Biol 55:225–261CrossRefPubMedGoogle Scholar
  23. Folkman J (2002) Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29:15–18CrossRefPubMedGoogle Scholar
  24. Ganai AA, Farooqi H (2015) Bioactivity of genistein: a review of in vitro and in vivo studies. Biomed Pharmacother 76:30–38CrossRefPubMedGoogle Scholar
  25. George VC, Dellaire G, Rupasinghe HV (2017) Plant flavonoids in cancer chemoprevention: role in genome stability. J Nutr Biochem 45:1–14CrossRefPubMedGoogle Scholar
  26. Giridharan P, Somasundaram S, Perumal K, Vishwakarma R, Karthikeyan N, Velmurugan R, Balakrishnan A (2002) Novel substituted methylenedioxy lignan suppresses proliferation of cancer cells by inhibiting telomerase and activation of c-myc and caspases leading to apoptosis. Br J Cancer 87:98–105CrossRefPubMedPubMedCentralGoogle Scholar
  27. Glazier MG, Bowman MA (2001) A review of the evidence for the use of phytoestrogens as a replacement for traditional estrogen replacement therapy. Arch Intern Med 161:1161–1172CrossRefPubMedGoogle Scholar
  28. Guillerey C, Smyth MJ (2015) NK cells and cancer immunoediting. Curr Top Microbiol Immunol 395:115–145Google Scholar
  29. Gupta SC, Kim JH, Prasad S, Aggarwal BB (2010) Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev 29:405–434CrossRefPubMedPubMedCentralGoogle Scholar
  30. Gupta C, Prakash D, Gupta S (2016) Phytoestrogens as pharma foods. Adv Food Technol Nutr Sci Open J 2:19–31CrossRefGoogle Scholar
  31. Haggar FA, Boushey RP (2009) Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg 22:191–197CrossRefPubMedPubMedCentralGoogle Scholar
  32. Hammond WA, Swaika A, Mody K (2016) Pharmacologic resistance in colorectal cancer: a review. Ther Adv Med Oncol 8:57–84CrossRefPubMedPubMedCentralGoogle Scholar
  33. Hausott B, Greger H, Marian B (2003) Naturally occurring lignans efficiently induce apoptosis in colorectal tumor cells. J Cancer Res Clin Oncol 129:569–576CrossRefPubMedGoogle Scholar
  34. Hedley BD, Chambers AF (2009) Tumor dormancy and metastasis. Adv Cancer Res 102:67–101CrossRefPubMedGoogle Scholar
  35. Howe GR, Benito E, Castelleto R, Cornée J, Estève J, Gallagher RP, Iscovich JM, Deng-Ao J, Kaaks R, Kune GA (1992) Dietary intake of fiber and decreased risk of cancers of the colon and rectum: evidence from the combined analysis of 13 case-control studies. J Natl Cancer Inst 84:1887–1896CrossRefPubMedGoogle Scholar
  36. Hussain H, Green IR (2017) A patent review of the therapeutic potential of isoflavones (2012–2016). Expert Opin Ther Pat 13:1339791.  https://doi.org/10.1080/13543776.2017.1339791 CrossRefGoogle Scholar
  37. Hwang KA, Choi KC (2015) Anticarcinogenic effects of dietary phytoestrogens and their chemopreventive mechanisms. Nutr Cancer 67:796–803CrossRefPubMedGoogle Scholar
  38. Hyder SM, Nawaz Z, Chiappetta C, Stancel GM (2000) Identification of functional estrogen response elements in the gene coding for the potent angiogenic factor vascular endothelial growth factor. Cancer Res 60:3183–3190PubMedGoogle Scholar
  39. Janout V, Kollarova H (2001) Epidemiology of colorectal cancer. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 145:5–10CrossRefPubMedGoogle Scholar
  40. Koehne CH, Dubois RN (2004) Cox-2 inhibition and colorectal cancer. Semin Oncol 2004:12–21CrossRefGoogle Scholar
  41. Krazeisen A, Breitling R, Möller G, Adamski J (2001) PE inhibit human 17β-hydroxysteroid dehydrogenase type 5. Mol Cell Endocrinol 171:151–162CrossRefPubMedGoogle Scholar
  42. Kurzer MS, Xu X (1997) Dietary phytoestrogens. Annu Rev Nutr 17:353–381CrossRefPubMedGoogle Scholar
  43. Larsson SC, Wolk A (2006) Meat consumption and risk of colorectal cancer: a meta-analysis of prospective studies. Int J Cancer 119:2657–2664CrossRefPubMedGoogle Scholar
  44. Leary RJ, Lin JC, Cummins J, Boca S, Wood LD, Parsons DW, Jones S, Sjoblom T, Park BH, Parsons R, Willis J, Dawson D, Willson JK, Nikolskaya T, Nikolsky Y, Kopelovich L, Papadopoulos N, Pennacchio LA, Wang TL, Markowitz SD, Parmigiani G, Kinzler KW, Vogelstein B, Velculescu VE (2008) Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers. Proc Natl Acad Sci U S A 105:16224–16229CrossRefPubMedPubMedCentralGoogle Scholar
  45. Lechner D, Kállay E, Cross HS (2005) Phytoestrogens and colorectal cancer prevention. Vitam Horm 70:169–198CrossRefPubMedGoogle Scholar
  46. Lee GA, Hwang KA, Choi KC (2016) Roles of dietary phytoestrogens on the regulation of epithelial-mesenchymal transition in diverse cancer metastasis. Toxins 8:E162.  https://doi.org/10.3390/toxins8060162 CrossRefPubMedGoogle Scholar
  47. Li Y, Ahmed F, Ali S, Philip PA, Kucuk O, Sarkar FH (2005) Inactivation of nuclear factor κB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells. Cancer Res 65:6934–6942CrossRefPubMedGoogle Scholar
  48. Li HQ, Luo Y, Qiao CH (2012) The mechanisms of anticancer agents by genistein and synthetic derivatives of isoflavone. Mini Rev Med Chem 12:350–362CrossRefPubMedGoogle Scholar
  49. Lin JK, Chang SC, Yang YC, Li AF (2003) Loss of heterozygosity and DNA aneuploidy in colorectal adenocarcinoma. Ann Surg Oncol 10:1086–1094CrossRefPubMedGoogle Scholar
  50. Mutanen M, Pajari AM, Oikarinen SI (2000) Beef induces and rye bran prevents the formation of intestinal polyps in apcmin mice: relation to β-catenin and pkc isozymes. Carcinogenesis 21:1167–1173CrossRefPubMedGoogle Scholar
  51. Mutoh M, Takahashi M, Fukuda K, Matsushima-Hibiya Y, Mutoh H, Sugimura T, Wakabayashi K (2000) Suppression of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells by chemopreventive agents with a resorcin-type structure. Carcinogenesis 21:959–963CrossRefPubMedGoogle Scholar
  52. Nishihara R, Wu K, Lochhead P, Morikawa T, Liao X, Qian ZR, Inamura K, Kim SA, Kuchiba A, Yamauchi M (2013) Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Eng J Med 369:1095–1105CrossRefGoogle Scholar
  53. Nogowski L (1999) Effects of phytoestrogen-coumestrol on lipid and carbohydrate metabolism in young ovariectomized rats may be independent of its estrogenicity. J Nutr Biochem 10:664–669CrossRefPubMedGoogle Scholar
  54. Noguchi K, Shitashige M, Yanai M, Morita I, Nishihara T, Murota S, Ishikawa I (1996) Prostaglandin production via induction of cyclooxygenase-2 by human gingival fibroblasts stimulated with lipopolysaccharides. Inflammation 20:555–568CrossRefPubMedGoogle Scholar
  55. Nüssler NC, Reinbacher K, Shanny N, Schirmeier A, Glanemann M, Neuhaus P, Nussler AK, Kirschner M (2008) Sex-specific differences in the expression levels of estrogen receptor subtypes in colorectal cancer. Gend Med 5:209–217CrossRefPubMedGoogle Scholar
  56. Oba S, Nagata C, Shimizu N, Shimizu H, Kametani M, Takeyama N, Ohnuma T, Matsushita S (2007) Soy product consumption and the risk of colon cancer: a prospective study in Takayama, Japan. Nutr Cancer 57:151–157CrossRefPubMedGoogle Scholar
  57. Ososki AL, Kennelly EJ (2003) Phytoestrogens: a review of the present state of research. Phytother Res 17:845–869CrossRefPubMedGoogle Scholar
  58. Pampaloni B, Mavilia C, Bartolini E, Tonelli F, Brandi M, Dasta F (2013) Phytoestrogens and colon cancer. In: El-Shemy H (ed) Soybean bioactive compounds. InTech. https://www.intechopen.com/books/soybean-bio-active-compounds/phytoestrogens-and-colon-cancer.  https://doi.org/10.5772/54065 Google Scholar
  59. Papadopoulos N, Nicolaides NC, Wei YF, Ruben SM, Carter KC, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM, Adams MD (1994) Mutation of a mutl homolog in hereditary colon cancer. Science 263:1625–1629CrossRefPubMedGoogle Scholar
  60. Park JH, Oh EJ, Choi YH, Kang CD, Kang HS, Kim DK, Kang KI, Yoo MA (2001) Synergistic effects of dexamethasone and genistein on the expression of Cdk inhibitor p21WAF1/CIP1 in human hepatocellular and colorectal carcinoma cells. Int J Oncol 18:997–1002PubMedGoogle Scholar
  61. Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas DB (2002) Cancer incidence in five continents. IARC Scientific Publications No. 155 vol, 8th edn. IARC, LyonGoogle Scholar
  62. Qi W, Weber CR, Wasland K, Roy H, Wali R, Joshi S, Savkovic SD (2011a) Tumor suppressor foxo3 mediates signals from the egf receptor to regulate proliferation of colonic cells. Am J Physiol Gastrointest Liver Physiol 300:264–272CrossRefGoogle Scholar
  63. Qi W, Weber CR, Wasland K, Savkovic SD (2011b) Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor foxo3 activity. BMC Cancer 11:219.  https://doi.org/10.1186/1471-2407-11-219 CrossRefPubMedPubMedCentralGoogle Scholar
  64. Rice S, Mason HD, Whitehead SA (2006) PE and their low dose combinations inhibit mrna expression and activity of aromatase in human granulosa-luteal cells. J Steroid Biochem Mol Biol 101:216–225CrossRefPubMedGoogle Scholar
  65. Rietjens IM, Louisse J, Beekmann K (2017) The potential health effects of dietary PE. Br J Pharmacol 174:1263–1280CrossRefPubMedGoogle Scholar
  66. Roper J, Hung KE (2013) Molecular mechanisms of colorectal carcinogenesis. Molecular pathogenesis of colorectal cancer. In: Haigis KM (ed) Molecular pathogenesis of colorectal cancer. Springer, New York, pp 25–65CrossRefGoogle Scholar
  67. Sakurai T, Kudo M (2011) Signaling pathways governing tumor angiogenesis. Oncology 81:S24–S29CrossRefGoogle Scholar
  68. Sandhu MS, Dunger DB, Giovannucci EL (2002) Insulin, insulin-like growth factor-i (Igf-i), Igf binding proteins, their biologic interactions, and colorectal cancer. J Natl Cancer Inst 94:972–980CrossRefPubMedGoogle Scholar
  69. Sarkar FH, Li Y (2003) Soy isoflavones and cancer prevention: clinical science review. Cancer Investig 21:744–757CrossRefGoogle Scholar
  70. Shafiee G, Saidijam M, Tavilani H, Ghasemkhani N, Khodadadi I (2016) Genistein induces apoptosis and inhibits proliferation of ht29 colon cancer cells. Int J Mol Cell Med 5:178–191PubMedPubMedCentralGoogle Scholar
  71. Shin A, Lee J, Lee J, Park MS, Park JW, Park SC, Oh JH, Kim J (2015) Isoflavone and soyfood intake and colorectal cancer risk: a case-control study in Korea. PLoS One 10:e0143228CrossRefPubMedPubMedCentralGoogle Scholar
  72. Smith G, Carey FA, Beattie J, Wilkie MJ, Lightfoot TJ, Coxhead J, Garner RC, Steele RJ, Wolf CR (2002) Mutations in apc, kirsten-ras, and p53-alternative genetic pathways to colorectal cancer. Proc Natl Acad Sci U S A 99:9433–9438CrossRefPubMedPubMedCentralGoogle Scholar
  73. Strum WB (2016) Colorectal adenomas. New Engl J Med 374:1065–1075CrossRefPubMedGoogle Scholar
  74. Sung M, Lautens M, Thompson L (1997) Mammalian lignans inhibit the growth of estrogen-independent human colon tumor cells. Anticancer Res 18:1405–1408Google Scholar
  75. Takayama T, Miyanishi K, Hayashi T, Sato Y, Niitsu Y (2006) Colorectal cancer: genetics of development and metastasis. J Gastroenterol 41:185–192CrossRefPubMedGoogle Scholar
  76. Tariq K, Ghias K (2016) Colorectal cancer carcinogenesis: a review of mechanisms. Cancer Biol Med 13:120–135CrossRefPubMedPubMedCentralGoogle Scholar
  77. Virk-Baker MK, Nagy TR, Barnes S (2010) Role of PE in cancer therapy. Planta Med 76:1132–1142CrossRefPubMedPubMedCentralGoogle Scholar
  78. Wang W, Liu LQ, Higuchi CM, Chen H (1998) Induction of NADPH: quinone reductase by dietary PE in colonic colo205 cells. Biochem Pharmacol 56:189–195CrossRefPubMedGoogle Scholar
  79. Wang Z, Cummins JM, Shen D, Cahill DP, Jallepalli PV, Wang TL, Parsons DW, Traverso G, Awad M, Silliman N (2004) Three classes of genes mutated in colorectal cancers with chromosomal instability. Cancer Res 64:2998–3001CrossRefPubMedGoogle Scholar
  80. Webb AL, Mccullough ML (2005) Dietary lignans: potential role in cancer prevention. Nutr Cancer 51:117–131CrossRefPubMedGoogle Scholar
  81. Williams C, Dileo A, Niv Y, Gustafsson JA (2016) Estrogen receptor beta as target for colorectal cancer prevention. Cancer Lett 372:48–56CrossRefPubMedGoogle Scholar
  82. Wiseman M (2008) The second world cancer research fund/American institute for cancer research expert report. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Proc Nutr Soc 67:253–256CrossRefPubMedGoogle Scholar
  83. Yang G, Shu XO, Li H, Chow WH, Cai H, Zhang X, Gao YT, Zheng W (2009) Prospective cohort study of soy food intake and colorectal cancer risk in women. Am J Clin Nutr 89:577–583CrossRefPubMedGoogle Scholar
  84. Yu H, Rohan T (2000) Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 92:1472–1489CrossRefPubMedGoogle Scholar
  85. Zauber AG, Winawer SJ, O’brien MJ, Lansdorp-Vogelaar I, Van Ballegooijen M, Hankey BF, Shi W, Bond JH, Schapiro M, Panish JF (2012) Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. New Engl J Med 366:687–696CrossRefPubMedGoogle Scholar
  86. Zhang B, Halder SK, Kashikar ND, Cho YJ, Datta A, Gorden DL, Datta PK (2010) Antimetastatic role of smad4 signaling in colorectal cancer. Gastroenterology 138:969–980CrossRefPubMedGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of BiochemistryNational Institute of NutritionHyderabadIndia

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