RESEARCH ARTICLE The effects of genistein and daidzein on cell proliferation kinetics in HT29 colon cancer cells: the expression of CTNNBIP1 (b-catenin), APC (adenomatous polyposis coli) and BIRC5 (survivin) Sandra Regina Lepri • Leonardo Campos Zanelatto • Patrı ´cia Benites Gonc ¸alves da Silva • Daniele Sartori • Lucia Regina Ribeiro • Mario Sergio Mantovani Received: 4 May 2012 / Accepted: 15 October 2012 / Published online: 4 January 2014 Ó Japan Human Cell Society and Springer Japan 2014 Abstract Soybean isoflavonoids have received signifi- cant 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 soy- bean 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 lM, 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 lM genistein, there was suppressed expression of b-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 lM. These data suggest that the down-regulation of b-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. Keywords Genistein Á Daidzein Á Proliferation kinetics Á b-catenin Á Surviving Á APC Á HT29 cell Introduction Dietary chemoprevention agents have received significant attention in the area of cancer research. It is estimated that one-third of all cancers could be prevented simply by eating a healthy diet, maintaining an ideal body weight, and participating in regular physical activity [1]. Because of the association of Japanese and Chinese diets with lower rates of many forms of cancer, such as breast, prostate, and colon, investigators have assumed that this phenomenon is due to soy food consumption [2]. Isoflavones are a class of organic compounds that have been found in large quantities in the soybean. In various experimental models, isoflavones have exhibited properties that suggest that they reduce cancer risk, including its ability to decrease cell prolifera- tion and induce apoptosis [2–4]. In addition, flavonoids themselves are believed to have little to no toxicity, and they have a long history of human consumption, making them excellent candidates for chemopreventive agents [4]. The canonical Wnt/b-catenin pathway comprises a large number of growth factors that are involved in the control of cell growth, differentiation, and apoptosis [5, 6]. The intracellular affecting this pathway is mediated by inducing degradation of cytoplasm b-catenin through the destruction complex of pro- teins including axin, adenomatous polyposis coli (APC) and glycogen synthase kinase-3b (GSK-3b)[5, 7, 8]. Aberrant signaling involving stabilization of b-catenin and its nuclear translocation is a significant stimulation of cell division, the consequence of the positive action of b-catenin nuclear for the expression of other proteins which play an important role in cell division, including cyclin D1, c-myc, and Cox-2 [7–9]. S. R. Lepri (&) Á L. C. Zanelatto Á P. B. G. da Silva Á D. Sartori Á M. S. Mantovani General Biology Department, State University of Londrina (UEL), Rodovia Celso Garcia Cid, Pr 445 km 380, Campus Universita ´rio, Cx. Postal 6001, CEP 86051-980 Londrina, PR, Brazil e-mail: lepri@uel.br L. R. Ribeiro Institute of Biosciences, Sa ˜o Paulo State University, UNESP, Campus de Botucatu - Distrito de Rubia ˜o Ju ´nior, S/ N - CEP 18618-970 Botucatu, SP, Brazil e-mail: lribeiro@fmb.unesp.br 123 Human Cell (2014) 27:78–84 DOI 10.1007/s13577-012-0051-6