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The effects of genistein and daidzein on cell proliferation kinetics in HT29 colon cancer cells: the expression of CTNNBIP1 (β-catenin), APC (adenomatous polyposis coli) and BIRC5 (survivin)

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Abstract

Soybean isoflavonoids have received significant attention due to their potential anticarcinogenic and antiproliferative effects and possible role in many signal transduction pathways. However, their mechanisms of action and their molecular targets remain to be further elucidated. In this paper, we demonstrated that two soybean isoflavones (genistein and daidzein) reduced the proliferation of the human colon adenocarcinoma grade II cell line (HT-29) at concentrations of 25 and 50–100 μM, respectively. We then investigated the effects of genistein and daidzein by RT-PCR on molecules that involved in tumor development and progression by their regulation of cell proliferation. At a concentration of 50 μM genistein, there was suppressed expression of β-catenin (CTNNBIP1). Neither genistein nor daidzein affected APC (adenomatous polyposis coli) or survivin (BIRC5) expression when cells were treated with concentrations of 10 or 50 μM. These data suggest that the down-regulation of β-catenin by genistein may constitute an important determinant of the suppression of HT-29 cell growth and may be exploited for the prevention and treatment of colon cancer.

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References

  1. American Cancer Society. Cancer Facts & Figures 2009. Atlanta: American Cancer Society; 2009.

  2. Birt DF, Hendrich S, Wang W. Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacol Ther. 2001;90:157–77.

    Article  PubMed  CAS  Google Scholar 

  3. Sarkar FH, Li Y. Cell signaling pathways altered by natural chemopreventive agents. Mutat Res. 2004;555:53–64.

    Article  PubMed  CAS  Google Scholar 

  4. Moon YJ, Wang X, Morris ME. Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro. 2006;20:187–210.

    Article  PubMed  CAS  Google Scholar 

  5. Polakis P. Wnt signaling and cancer. Genes Dev. 2000;14:1837–51.

    PubMed  CAS  Google Scholar 

  6. Mariadason JM, Bordonaro M, Aslam F, Shi L, Kuraguchi M, Velcich A, Augenlicht LH. Down-regulation of b-catenin TCF signaling is linked to colonic epithelial cell differentiation. Cancer Res. 2001;61:3465–71.

    PubMed  CAS  Google Scholar 

  7. Luu HH, Zhang R, Haydon RC, Rayburn E, Kang Q, Si W, Park JK, Wang H, Peng Y, Jiang W, He TC. Wnt/β-catenin signaling pathway as novel cancer drug targets. Curr Cancer Drug Targets. 2004;4:653–71.

    Article  PubMed  CAS  Google Scholar 

  8. Pinho MSL. A Estória Biomolecular Do Pólipo Adenomatoso. Rev bras Coloproct. 2006;26(2):197–203.

    Article  Google Scholar 

  9. Yang M, Zhong WW, Srivastava N, Slavin A, Yang J, Hoey T, An S. G protein-coupled lysophosphatidic acid receptors stimulate proliferation of colon cancer cells through the β-catenin pathway. Proc Natl Acad Sci USA. 2005;102:6027–32.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Zhang T, Otevrel T. Gao Zhengiang, Gao Zhiping, Ehrlich SM, Fields JZ, Boman BM. Evidence that APC regulates survivin expression: a possible mechanism contributing to the stem cell origin of colon cancer. Cancer Res. 2001;62:8664–7.

    Google Scholar 

  11. Kim PJ, Plescia J, Clevers H, Fearon ER, Altieri DC. Survivin and molecular pathogenesis of colorectal cancer. Lancet. 2003;362:205–9.

    Article  PubMed  CAS  Google Scholar 

  12. Altieri DC. The molecular basis and potential role of survivin in cancer diagnosis and therapy. Trends Mol Med. 2001;7(12):542–7.

    Article  PubMed  CAS  Google Scholar 

  13. Chandra SHV, Wacker I, Appelt, UK, Behrens J, Schneikert J. A common role for various human truncated adenomatous polyposis coli isoforms in the control of beta-catenin activity and cell proliferation. PLoS ONE. 2012;7(4):e34479. doi:10.1371/journal.pone.0034479.

  14. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29(9):2002–7.

    Article  Google Scholar 

  15. Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002;30(9):e36.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Kanadaswami C, Lee LT, Lee PPH, Hwang JJ, Ke FC, Huang YT, Lee MT. The antitumor activities of flavonoids. In vivo. 2005;19:895–910.

    PubMed  CAS  Google Scholar 

  17. Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: promising anticancer agents. Med Res Rev. 2003;23(4):519–34.

    Article  PubMed  CAS  Google Scholar 

  18. Kuntz S, Wenzel U, Daniel H. Comparative analysis of the effect of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines. Eur J Nutr. 1999;38:133–42.

    Article  PubMed  CAS  Google Scholar 

  19. Chen WF, Huangc MH, Tzangc CH, Yangc M, Wong MS. Inhibitory actions of genistein in human breast cancer (MCF-7) cells. Biochim Biophys Acta. 2003;1638:187–96.

    Article  PubMed  CAS  Google Scholar 

  20. Wang H, Zhu Y, Li C, Xie L, Chen G, Nie Y, Zhang R. Effects of genistein on cell cycle and apoptosis of two murine melanoma cell lines. Tsinghua Sci Technol. 2007;12:372–80.

    Article  CAS  Google Scholar 

  21. Chodon D, Ramamurty NE, Sakthisekaran D. Preliminary studies on induction of apoptosis by genistein on HepG2 cell line. Toxicol In Vitro. 2007;21:887–91.

    Article  PubMed  CAS  Google Scholar 

  22. Choi EJ, Kim GH. Daidzein causes cell cycle arrest at the G1 and G2/M phases in human breast câncer MCF-7 and MDA-MB-453 cells. Phytomedicine. 2008;15:683–90.

    Article  PubMed  CAS  Google Scholar 

  23. Sergent T, Garsou S, Schaut A, De Saeger S, Pussemier L, Van Peteghem C, Larondelle Y, Schneider YJ. Differential modulation of ochratoxin A absorption across Caco-2 cells by dietary polyphenols, used at realistic intestinal concentrations. Toxicol Lett. 2005;159:60–70.

    Article  PubMed  CAS  Google Scholar 

  24. Narayan S, Roy D. Role of APC and DNA mismatch repair genes in the development of colorectal cancers. Mol Cancer. 2003;2:41.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Fearnhead NS, Britton MP, Bodmer WF. The ABC of APC. Hum Mol Genet. 2001;10(7):721–33.

    Article  PubMed  CAS  Google Scholar 

  26. Lee JH, Park CH, Jung KC, Rhee HS, Yang CH. Negative regulation of beta-catenin/Tcf signaling by naringenin in AGS gastric cancer cell. Biochem Biophys Res Commun. 2005;335:771–6.

    Article  PubMed  CAS  Google Scholar 

  27. Park CH, Hahm ER, Lee JH, Jung KC, Yang CH. Inhibition of beta-catenin-mediated transactivation by flavanone in AGS gastric cancer cells. Biochem Biophys Res Commun. 2005;331:1222–8.

    Article  PubMed  CAS  Google Scholar 

  28. Park CH, Chang JY, Hahm ER, Park S, Kim HK, Yang CH. Quercetin, a potent inhibitor against beta-catenin/Tcf signaling in SW480 colon cancer cells. Biochem Biophys Res Commun. 2005;328:227–34.

    Article  PubMed  CAS  Google Scholar 

  29. Li W, Wang Z, Kong D, Li R, Sarkar SH, Sarkar FH. Regulation of Akt/FOXO3a/GSK-3β/AR signaling network by isoflavone in prostate cancer cells. J Biol Chem. 2008;283(41):27707–16.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  30. Verma UN, Surabhi RM, Schmaltieg A, Becerra C, Gaynor RB. Small interfering RNAs directed against β-catenin inhibit the in vitro and in vivo growth of colon cancer cells. Clin Cancer Res. 2003;9:1291–300.

    PubMed  CAS  Google Scholar 

  31. Choi BR, Gwak J, Kwon HM, Oh S, Kim KP, Choi WH, Cho Y, Kim DE. Oligodeoxyribozymes that cleave β-catenin messenger rna inhibit growth of colon cancer cells via reduction of β-catenin response transcription. Mol Cancer Ther. 2010;9:1894–902.

    Article  PubMed  CAS  Google Scholar 

  32. Zhang T, Fields JZ, Opdenaker L, Otevrel T, Masuda E, Palazzo JP, Isenberg GA, Goldstein SD, Brand M, Boman BM. Survivin-induced aurora-B kinase activation. Am J Pathol. 2010;177(6):2816–26.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  33. Pennati M, Folini M, Zaffaroni N. Targeting survivin in cancer therapy: fulfilled promises and open questions. Carcinogenesis. 2007;28(6):1133–9.

    Article  PubMed  CAS  Google Scholar 

  34. Miao GY, Lu QM, Zhang XL. Downregulation of survivin by RNAi inhibits growth of human gastric carcinoma cells. World J Gastroenterol. 2007;13(8):1170–4.

    PubMed  CAS  Google Scholar 

  35. Shen YM, Yang YC, Song ML, Qin CH, Yang C, Sun YH. Growth inhibition induced by short hairpin RNA to silence survivin gene in human pancreatic cancer cells. Hepatobiliary Pancreat Dis Int. 2010;9:69–77.

    PubMed  CAS  Google Scholar 

  36. Weglarz L, Molin I, Orchel A, Parfiniewicz B, Dzierzewicz Z. Quantitative analysis of the level of p53 and p21WAF1 mRNA in human colon cancer HT-29 cells treated with inositol hexaphosphate. Acta Biochim Pol. 2006;53:349–356.

    Google Scholar 

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Acknowledgments

The authors thank the Araucária Foundation, CNPq, and CAPES.

Conflict of interest

The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

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Authors and Affiliations

  1. General Biology Department, State University of Londrina (UEL), Rodovia Celso Garcia Cid, Pr 445 km 380, Campus Universitário, Cx. Postal 6001, CEP 86051-980, Londrina, PR, Brazil

    Sandra Regina Lepri, Leonardo Campos Zanelatto, Patrícia Benites Gonçalves da Silva, Daniele Sartori & Mario Sergio Mantovani

  2. Institute of Biosciences, São Paulo State University, UNESP, Campus de Botucatu - Distrito de Rubião Júnior, S/N - CEP 18618-970, Botucatu, SP, Brazil

    Lucia Regina Ribeiro

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  1. Sandra Regina Lepri
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  2. Leonardo Campos Zanelatto
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Correspondence to Sandra Regina Lepri.

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Lepri, S.R., Zanelatto, L.C., da Silva, P.B.G. et al. The effects of genistein and daidzein on cell proliferation kinetics in HT29 colon cancer cells: the expression of CTNNBIP1 (β-catenin), APC (adenomatous polyposis coli) and BIRC5 (survivin). Human Cell 27, 78–84 (2014). https://doi.org/10.1007/s13577-012-0051-6

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  • DOI: https://doi.org/10.1007/s13577-012-0051-6

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