DOI QR코드

DOI QR Code

Quercetin Confers Tumoricidal Activity Through Multipathway Mechanisms in A N-Methylnitrosourea Rat Model of Colon Cancer

  • Ahmed, Hanaa H (Hormones Department, National Research Centre) ;
  • Aglan, Hadeer A (Hormones Department, National Research Centre) ;
  • Zaazaa, Asmaa M (Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University) ;
  • Shalby, Aziza B (Hormones Department, National Research Centre) ;
  • Toumy, Sayed A El (Chemistry of Tannins Department, National Research Centre)
  • 발행 : 2016.11.01

초록

Objective: This research was conducted to explore mechanisms behind the potency of quercetin in inhibiting colon cancer induced in an experimental model. Materials and Methods: Forty adult male rats of Wistar strain were distributed into 4 groups; a negative control group, a colon cancer bearing group, a quercetin-treated group and a 5-fluorouracil (5-FU)-treated group. Serum TAG72 and GAL3 levels were quantified by ELISA. Colonic Wnt5a and Axin-1 gene expression was estimated by PCR. In addition, colonic tissues were subjected to immunohistochemical examination of Bax expression and histological investigation of histopathological alterations. Results: Quercetin elicited significant reduction in serum TAG72 and GAL3 levels, in addition to significant suppression of colonic Wnt5a gene expression and amplification of colonic Axin-1 gene expression. Also, it caused moderate positive reaction for Bax in mucosal epithelium. Conclusion: The present research provides experimental evidence about the activity of quercetin in the colon cancer of rats. Inhibitory effects on cancer development might be ascribable to regulatory action on Wnt signaling and induction of apoptosis.

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참고문헌

  1. Agullo G, Gamet L, Besson C, Demigne C, Remesy C (1994). Quercetin exerts a preferential cytotoxic effect on active dividing colon carcinoma HT29 and CaCO2 cells. Cancer Lett, 87, 55-63. https://doi.org/10.1016/0304-3835(94)90409-X
  2. Ahmed H, Banerjee PP, Vasta GR (2007). Differential expression of galectins in normal, benign and malignant prostate epithelial cells: silencing of galectin-3 expression in prostate cancer by its promoter methylation. Biochem Biophys Res Commun, 358, 241-6. https://doi.org/10.1016/j.bbrc.2007.04.114
  3. Ahmed HH, Shousha WGh, El-Mezayen HA, El-Toumy SA, Ramadan AR (2015): Updates on the biochemical and molecular mechanisms of N-nitrosodiethylamine-induced hepatocellular carcinoma: promising therapeutic role of Punica granatum peel extract. Int J Pharm Sci Rev Res, 32, 121-44.
  4. Asao T, Takayuki A, Shibata HR, Batist G, Brodt P (1992). Eradication of hepatic metastases of carcinoma H-59 combination chemoimmunotherapy with liposomal muramyl tripeptide, 5-fluorouracil, and leucovorin. Cancer Res, 52, 6254-7.
  5. Bafico A, Liu G, Goldin L, Harris V, Aaronson SA (2004). An autocrine mechanism for constitutive Wnt pathway activation in human cancer cells. Cancer Cell, 6, 497-506. https://doi.org/10.1016/j.ccr.2004.09.032
  6. Balaji C, Muthukumaran J, Nalini N (2014). Chemopreventive effect of sinapic acid on 1,2-dimethylhydrazineinduced experimental rat colon carcinogenesis. Hum Exp Toxicol, 33, 1253-68. https://doi.org/10.1177/0960327114522501
  7. Banchroft JD, Stevens A, Turner DR (1996). Theory and practice of histological techniques. 4thEd. Churchill Livingstone, Philadelphia, USA pp 25-90.
  8. Bancroft JD, Gamble M (2008). Theory and practice of histological techniques. 6th Ed. Churchill Livingstone, Philadelphia, USA pp 433-69.
  9. Barker N, Clevers H (2006). Mining the Wnt pathway for cancer therapeutics. Nat Rev Drug Discov, 5, 997-1014. https://doi.org/10.1038/nrd2154
  10. Bulzomi P, Galluzzo P, Bolli A, et al (2012). The pro-apoptotic effect of quercetin in cancer cell lines requires $ER{\beta}$-dependent signals. J Cell Physiol, 227, 1891-8. https://doi.org/10.1002/jcp.22917
  11. Cappell MS (2007). From colonic polyps to colon cancer: pathophysiology, clinical presentation, screening and colonoscopic therapy. Minerva Gastroenterol Dietol, 53, 351-73.
  12. Chao DT, Korsmeyer SJ (1998). BCL-2 family: regulators of cell death. Annu Rev Immunol, 16, 395-419. https://doi.org/10.1146/annurev.immunol.16.1.395
  13. Chen W, Lin M, Zhang B, et al (2007). Survey of molecular profiling during human colon cancer development and progression by immunohistochemical staining on tissue microarray. World J Gastroenterol, 13, 699-708. https://doi.org/10.3748/wjg.v13.i5.699
  14. Cheong T, Shin J, Chun K (2010). Silencing of galectin-3 changes the gene expression and augments the sensitivity of gastric cancer cells to chemotherapeutic agents. Cancer Sci, 101, 94-102. https://doi.org/10.1111/j.1349-7006.2009.01364.x
  15. Chien AJ, Moon RT (2007). WNTs and WNT receptors as therapeutic tools and targets in human disease processes. Front Biosci, 12, 448-57. https://doi.org/10.2741/2074
  16. Clements WM, Lowy AM, Groden J (2003). Adenomatous polyposis coli/beta-catenin interaction and downstream targets: altered gene expression in gastrointestinal tumors. Clin Colorectal Cancer, 3, 113-20. https://doi.org/10.3816/CCC.2003.n.018
  17. Clevers H (2006). Wnt/beta-catenin signaling in development and disease. Cell, 127, 469-80. https://doi.org/10.1016/j.cell.2006.10.018
  18. Csokay B, Pradja N, Weber G, Olah E (1997). Molecular mechanisms in the antiproliferative action of quercetin. Life Sci, 60, 2157-63. https://doi.org/10.1016/S0024-3205(97)00230-0
  19. Damdinsuren B, Nagano H, Wada H, et al (2007). Interferon alpha receptors are important for antiproliferative effect of interferon-alpha against human hepatocellular carcinoma cells. Hepatol Res, 37, 77- 83. https://doi.org/10.1111/j.1872-034X.2007.00007.x
  20. Duthie GG, Duthie SJ, Kyle JA (2000). Plant polyphenols in cancer and heart disease: implications as nutritional antioxidants. Nutr Res Rev, 13, 79-106. https://doi.org/10.1079/095442200108729016
  21. Eguchi H, Nagano H, Yamamoto H, et al (2000). Augmentation of antitumor activity of 5-fluorouracil by interferon alpha is associated with up-regulation of p27Kip1 in human hepatocellular carcinoma cells. Clin Cancer Res, 6, 2881-90.
  22. Endo H, Hosono K, Fujisawa T, et al (2009). Involvement of JNK pathway in the promotion of the early stage of colorectal carcinogenesis under high-fat dietary conditions. Gut, 58, 1637-43. https://doi.org/10.1136/gut.2009.183624
  23. Endo K, Kohnoe S, Tsujita E, et al (2005). Galectin-3 expression is a potent prognostic marker in colorectal cancer. Anticancer Res, 25, 3117-21.
  24. Galluzzo P, Martini C, Bulzomi P, et al (2009). Quercetin induced apoptotic cascade in cancer cells: Antioxidant versus estrogen receptor a dependent mechanisms. Mol Nutr Food Res, 53, 699-708. https://doi.org/10.1002/mnfr.200800239
  25. Gellad ZF, Provenzale D (2010). Colorectal cancer: national and international perspective on the burden of disease and public health impact. Gastroenterology, 138, 2177-90. https://doi.org/10.1053/j.gastro.2010.01.056
  26. Greco C, Vona R, Cosimelli M, et al (2004). Cell surface overexpression of galectin-3 and the presence of its ligand 90k in the blood plasma as determinants in colon neoplastic lesions. Glycobiology, 14, 783-92. https://doi.org/10.1093/glycob/cwh092
  27. Guadagni F, Roselli M, Cosimelli M, et al (1996). TAG-72 expression and its role in the biological evaluation of human colorectal cancer. Anticancer Res, 16, 2141-8.
  28. Harborne JB (1984). Phytochemical methods. 2nd Ed, Chapman and Hall, London pp 1-36.
  29. He XT, Fan XM, Zha XL (2011). Ghrelin inhibits 5-fluorouracil- induced apoptosis in colonic cancer cells. J Gastroenterol Hepatol, 26, 1169-73. https://doi.org/10.1111/j.1440-1746.2011.06715.x
  30. Hughes RC (2001). Galectins as modulators of cell adhesion. Biochimie, 83, 667-76. https://doi.org/10.1016/S0300-9084(01)01289-5
  31. Iurisci I, Tinari N, Natoli C, et al (2000). Concentrations of galectin-3 in the sera of normal controls and cancer patients. Clin Cancer Res, 6, 1389-93.
  32. Katoh M (2003). Expression and regulation of WNT1 in human cancer: up-regulation of WNT1 by beta-estradiol in MCF-7 cells. Int J Oncol, 22, 209-12.
  33. Kikuchi A (1999). Roles of Axin in the Wnt signalling pathway. Cell Signal, 11, 777-88. https://doi.org/10.1016/S0898-6568(99)00054-6
  34. Kim HP, Son KH, Chang HW, Kang SS (2004). Anti-inflammatory plant flavonoids and cellular action mechanisms. J Pharmacol Sci, 96, 229-45. https://doi.org/10.1254/jphs.CRJ04003X
  35. Kim JY, Kim EH, Park SS, et al (2008). Quercetin sensitizes human hepatoma cells to TRAIL-induced apoptosis via Sp1-mediated DR5 up-regulation and proteasome-mediated c-FLIPS down-regulation. J Cell Biochem, 105, 1386-98. https://doi.org/10.1002/jcb.21958
  36. Kiss R, Dubois J (2011). Quercetin inhibits a large panel of kinases implicated in cancer cell biology. Int J Oncol, 38, 833-42.
  37. Klaus A, Birchmeier W (2008). Wnt signalling and its impact on development and cancer. Nat Rev Cancer, 8, 387-98. https://doi.org/10.1038/nrc2389
  38. Kondo M, Nagano H, Wada H, et al (2005). Combination of IFN-alpha and 5-fluorouracil induces apoptosis through IFN-alpha/beta receptor in human hepatocellular carcinoma cells. Clin Cancer Res, 11, 1277-86.
  39. Kuo PC, Liu HF, Chao JI (2004). Survivin and p53 modulate quercetin-induced cell growth inhibition and apoptosis in human lung carcinoma cells. J Biol Chem, 279, 55875-985. https://doi.org/10.1074/jbc.M407985200
  40. Lee JS, Ishimoto A, Yanagawa S (1999). Characterization of mouse disheveled (Dvl) proteins in Wnt/Wingless signaling pathway. J Biol Chem, 274, 21464-70. https://doi.org/10.1074/jbc.274.30.21464
  41. Logan CY, Nusse R (2004). The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol, 20, 781-810. https://doi.org/10.1146/annurev.cellbio.20.010403.113126
  42. Lu H, Peng T, Hu X, et al (2015). Quercetin potentiates the effect of ${\gamma}{\delta}$ T cells via modulating the expressions of Granzyme B, perforin and IFN-$\gamma$ and also regulates the Wnt/${\beta}$-catenin signalling pathway in human colon cancer cells. Bangladesh J Pharmacol, 10, 251-9. https://doi.org/10.3329/bjp.v10i2.20387
  43. Mabry TJ, Markham KR, Thomas MB (1970). The Systematic identification of flavonoids, Springer, Verlag and New York pp 35-109.
  44. Markham KR (1982). Techniques of flavonoid identification, Academic Press, London pp 1-113.
  45. Mense SM, Hei TK, Ganju RK, Bhat HK (2008). Phytoestrogens and breast cancer prevention: Possible mechanisms of action. Environ Health Perspect, 116, 426-33. https://doi.org/10.1289/ehp.116-a426
  46. Nagano H, Miyamoto A, Wada H, et al (2007). Interferon-alpha and 5-fluorouracil combination therapy after palliative hepatic resection in patients with advanced hepatocellular carcinoma, portal venous tumor thrombus in the major trunk, and multiple nodules. Cancer, 110, 2493-501. https://doi.org/10.1002/cncr.23033
  47. Nakahara S, Raz A (2007). Regulation of cancer-related gene expression by galectin-3 and the molecular mechanism of its nuclear import pathway. Cancer Metastasis Rev, 26, 605-10. https://doi.org/10.1007/s10555-007-9095-6
  48. Nakamura M, Nagano H, Sakon M, et al (2007). Role of the Fas/FasL pathway in combination therapy with interferon-alpha and fluorouracil against hepatocellular carcinoma in vitro. J Hepatol, 46, 77-88. https://doi.org/10.1016/j.jhep.2006.07.032
  49. Narayanan BA, Geoffroy O, Willingham MC, Re GG, Nixon DW (1999). p53/p21 WAF1/CIP1 expression and its possible role in G1 arrest and apoptosis in ellagic acid treated cancer cells. Cancer Lett, 136, 215-21. https://doi.org/10.1016/S0304-3835(98)00323-1
  50. Narisawa T, Fukaura Y (2003). Prevention by intrarectal 5-aminosalicylic acid of N-methylnitrosourea-induced colon cancer in F344 rats. Dis Colon Rectum, 46, 900-3. https://doi.org/10.1007/s10350-004-6681-3
  51. Nguyen TT, Tran E, Nguyen TH, et al (2004). The role of activated MEK-ERK pathway in quercetin-induced growth inhibition and apoptosis in A549 lung cancer cells. Carcinogenesis, 25, 647-59.
  52. Noda T, Nagano H, Takemasa L, et al (2009). Activation of Wnt/b-catenin signalling pathway induces chemoresistance to interferon-a/5-fluorouracil combination therapy for hepatocellular carcinoma. Br J Cancer, 100, 1647-58. https://doi.org/10.1038/sj.bjc.6605064
  53. Orford K, Crockett C, Jensen JP, Weissman AM, Byers SW (1997). Serine phosphorylation-regulated biquitination and degradation of beta-catenin. J Biol Chem, 272, 24735-8. https://doi.org/10.1074/jbc.272.40.24735
  54. Ousingsawat J, Spitzner M, Puntheeranurak S, et al (2007). Expression of voltage-gated potassium channels in human and mouse colonic carcinoma. Clin Cancer Res, 13, 824-31. https://doi.org/10.1158/1078-0432.CCR-06-1940
  55. Park C, Chang JY, Hahm ER, et al (2005). Quercetin, a potent inhibitor against ${\beta}$-catenin/Tcf signaling in SW480 colon cancer cells. Biochem Biophys Res Commun, 328, 227-34. https://doi.org/10.1016/j.bbrc.2004.12.151
  56. Paul S, Kundu R (2013). Antiproliferative activity of methanolic extracts from two green algae, Enteromorpha intestinalis and Rizoclonium riparium on HeLa cells. DARU, 21, 1-12. https://doi.org/10.1186/2008-2231-21-1
  57. Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC (2000). An LDL-receptor-related protein mediates Wnt signalling in mice. Nature, 407, 535-8. https://doi.org/10.1038/35035124
  58. Plaumann B, Fritsche M, Rimpler H, Brandner G, Hess RD (1996). Flavonoids activate wild type p53. Oncogene, 13, 1605-14.
  59. Puglisi F, Minisini AM, Barbone F, et al (2004). Galectin-3 expression in non-small cell lung carcinoma. Cancer Lett, 212, 233-9. https://doi.org/10.1016/j.canlet.2004.03.006
  60. Raftery L, Goldberg RM (2010). Optimal delivery of cytotoxic chemotherapy for colon cancer. Cancer J, 16, 214-9. https://doi.org/10.1097/PPO.0b013e3181ddc5ac
  61. Rajamanickam S, Agarwal R (2008). Natural products and colon cancer: current status and future prospects. Drug Dev Res, 69, 460-71. https://doi.org/10.1002/ddr.20276
  62. Ramos S (2008). Cancer chemoprevention and chemotherapy, dietary polyphenols and signalling pathways. Mol Nutr Food Res, 52, 507-52. https://doi.org/10.1002/mnfr.200700326
  63. Rampone B, Schiavone B, Martino A, Confuorto G (2010). Current role of hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis from colorectal cancer. World J Gastroenterol, 16, 1299-1302. https://doi.org/10.3748/wjg.v16.i11.1299
  64. Reya T, Clevers H (2005). Wnt signalling in stem cells and cancer. Nature, 434, 843-50. https://doi.org/10.1038/nature03319
  65. Sadik NA, Shaker OG (2013). Inhibitory effect of a standardized pomegranate fruit extract onwnt signalling in 1,2-dimethylhydrazine induced rat colon carcinogenesis. Dig Dis Sci, 58, 2507-17. https://doi.org/10.1007/s10620-013-2704-z
  66. Scambia G, Panici PB, Ranelletti FO, et al (1994). Quercetin enhances transforming growth factor beta 1 secretion by human ovarian cancer cells. Int J Cancer, 57, 211-5. https://doi.org/10.1002/ijc.2910570214
  67. Seeram NP (2008). Berry fruits for cancer prevention: current status and future prospects. J Agric Food Chem, 55, 630-5.
  68. Song L, Tang JW, Owusu L, et al (2014). Galectin-3 in cancer. Clin Chim Acta, 431, 185-91. https://doi.org/10.1016/j.cca.2014.01.019
  69. Steinberg P (2010). The role of inflammation in colon cancer induced by food contaminants. Toxicology Lett, 196, 5-6.
  70. Stevenson DE, Hurst RD (2007). Polyphenolic phytochemicals-just antioxidants or much more?. Cell Mol Life Sci, 64, 2900-16. https://doi.org/10.1007/s00018-007-7237-1
  71. Stoner GD (2009). Foodstuffs for preventing cancer: the preclinical and clinical development of berries. Cancer Prev Res, 2, 187-94. https://doi.org/10.1158/1940-6207.CAPR-08-0226
  72. Uddin S, Choudhry MA (1995). Quercetin, a bioflavonoid, inhibits the DNA synthesis of human leukemia cells. Biochem Mol Biol Int, 36, 545-50.
  73. van Duijnhoven FJ, Bueno-De-Mesquita HB, Ferrari P, et al (2009). Fruit, vegetables, and colorectal cancer risk: the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr, 89, 1441-52. https://doi.org/10.3945/ajcn.2008.27120
  74. Vijayababu MR, Arunkumar A, Kanagaraj P, et al (2006). Quercetin downregulates matrix metalloproteinases 2 and 9 proteins expression in prostate cancer cells (PC-3). Mol Cell Biochem, 287, 109-16. https://doi.org/10.1007/s11010-005-9085-3
  75. Wada H, Nagano H, Yamamoto H, et al (2007). Combination therapy of interferon alpha and 5-fluorouracil inhibits tumor angiogenesis in human hepatocellular carcinoma cells by regulating vascular endothelial growth factor and angiopoietins. Oncol Rep, 18, 801-9.
  76. Yamamoto T, Nagano H, Sakon M, et al (2004). Partial contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of interferonalpha/5-fluorouracil against Hepatocellular Carcinoma. Clin Cancer Res, 10, 7884-95. https://doi.org/10.1158/1078-0432.CCR-04-0794
  77. Zamin LL, Filippi-Chiela EC, Vargas J, et al (2014). Quercetin promotes glioma growth in a rat model. Food Chem Toxicol, 63, 205-11. https://doi.org/10.1016/j.fct.2013.11.002
  78. Zhang N, Ding YQ, Liang L (2006). Association of galectin-3 expression with biological behaviors of human colorectal carcinoma. Nanfang Yikedaxue Xuebao, 26, 1685-9.
  79. Zheng Z, Cheng K, Chao J, Wu J, Wang M (2008). Tyrosinase inhibitors from Paper Mulberry (Broussonetia Papyrifera). Food Chem, 106, 529-35. https://doi.org/10.1016/j.foodchem.2007.06.037
  80. Zou J, Glinsky VV, Landon LA, Matthews L, Deutscher SL (2005). Peptides specific to the galectin-3 carbohydrate recognition domain inhibit metastasis-associated cancer cell adhesion. Carcinogenesis, 26, 309-18.