- Open Access
Genistein inhibits the contact-stimulated migration of prostate cancer cells
Cellular & Molecular Biology Lettersvolume 12, Article number: 348 (2007)
The results of several epidemiological studies have suggested that a soybean-based diet is associated with a lower risk of prostate cancer. We investigated the effect of the soy isoflavone genistein on the proliferation and contact-stimulated migration of rat prostatic carcinoma MAT-LyLu and AT-2 cell lines. Genistein almost completely inhibited the growth of both MAT-LyLu and AT-2 cells in the concentration range from 25 to 100 μM, but the addition of 1 μM genistein to the medium significantly stimulated the proliferation of both cell lines. Additionally, at concentrations above 25 μM, genistein showed a potent cytotoxic effect. However, the central finding of this study is that at physiologically relevant concentrations (1 μM and 10 μM), genistein inhibits the motility of prostate cancer cells stimulated by homo-and heterotypic contacts. These results show that at physiological concentrations, genistein exerts an inhibitory effect on the migration of prostate cancer cells and suggest that it may be one of the factors responsible for the anti-metastatic activity of plant isoflavonoids
coefficient of movement efficiency
fetal calf serum
Messina, M.J., Persky, V., Setchell, K.D. and Barnes, S. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr. Cancer 21 (1994) 113–131.
Pollard, M. and Luckert, P.H. Influence of isoflavones in soy protein isolates on development of induced prostate-related cancers in L-W rats. Nutr. Cancer 28 (1997) 41–45.
Shen, J.C., Klein, R.D., Wei, Q., Guan, Y., Contois, J.H., Wang, T.T., Chang, S. and Hursting, S.D. Low-dose genistein induces cyclin-dependent kinase inhibitors and G(1) cell-cycle arrest in human prostate cancer cells. Mol. Carcinog. 29 (2000) 92–102.
Severson, R.K., Nomura, A.M., Grove, J.S. and Stemmermann, G.N. A prospective study of demographics, diet, and prostate cancer among men of Japanese ancestry in Hawaii. Cancer Res. 49 (1989) 1857–1860.
Schleicher, R.L., Lamartiniere, C.A., Zheng, M. and Zhang, M. The inhibitory effect of genistein on the growth and metastasis of a transplantable rat accessory sex gland carcinoma. Cancer Lett. 136 (1999) 195–201.
Liu, Y., Kyle, E., Lieberman, R., Crowell, J., Kellof, G. and Bergan, R.C. Focal adhesion kinase (FAK) phosphorylation is not required for genisteininduced FAK-beta-1-integrin complex formation. Clin. Exp. Metastasis 18 (2000) 203–212.
Valachovicova, T., Slivova, V., Bergman, H., Shuherk, J. and Sliva, D. Soy isoflavones suppress invasiveness of breast cancer cells by the inhibition of NF-kappaB/AP-1-dependent and-independent pathways. Int. J. Oncol. 25 (2004)1389–1395.
Iishi, H., Tatsuta, M., Baba, M., Yano, H., Sakai, N. and Akedo, H. Genistein attenuates peritoneal metastasis of azoxymethane-induced intestinal adenocarcinomas in Wistar rats. Int. J. Cancer 86 (2000) 416–420.
Chambers, A.F. The metastatic process: basic research and clinical implications. Oncology Res. 11 (1999) 161–168.
Grimstad, I.A. Direct evidence that cancer cell locomotion contributes importantly to invasion. Exp. Cell. Res. 173 (1987) 515–523.
Stracke, M.L., Aznavoorian, S.A., Beckner, M.E., Liotta, L.A. and Schiffmann, E. Cell motility, a principal requirement for metastasis. in: Cell Motility Factors, (Goldberg, I.D., Ed.), Birkhauser Verlag, Basel, 1991, 147–162.
Aznavoorian, S., Stracke, M.L., Krutzsch, H., Schiffmann, E. and Liotta, L.A. Signal transduction for chemotaxis and haptotaxis by matrix molecules in tumor cells. J. Cell Biol. 110 (1990) 1427–1438.
Korohoda, W. and Madeja, Z. Contact of sarcoma cells with aligned fibroblasts accelerates their displacement: computer-assisted analysis of tumour cell locomotion in co-culture. Biochem. Cell Biol. 75 (1997) 263–276.
Djamgoz, M.B.A., Mycielska, M., Madeja, Z., Fraser, S.P. and Korohoda, W. Directional movement of rat prostate cancer cells in electric field: Control by voltage-gated Na+ channel activity. J. Cell Sci. 114 (2000) 12697–12705.
Madeja, Z., Miękus, K., Sroka, J., Djamgoz, M.B.A. and Korohoda, W. Homotypic cell-cell contacts stimulate the motile activity of rat prostate cancer cells. Br. J. Urol. Int. 88 (2001a) 776–786.
Madeja, Z., Szymkiewicz, I., Żaczek, A., Sroka, J., Miękus, K. and Korohoda, W. Contact-activated migration of melanoma B16 and sarcoma XC cells. Biochem. Cell Biol. 79 (2001b) 425–440.
Miekus, K., Czernik, M., Sroka, J., Czyz, J. and Madeja, Z. Contact stimulation of prostate cancer cell migration: the role of gap junctional coupling and migration stimulated by heterotypic cell-to-cell contacts in determination of the metastatic phenotype of Dunning rat prostate cancer cells. Biol. Cell 97 (2005) 893–903.
Madeja, Z. and Sroka, J. Contact guidance of Walker carcinosarcoma cells by the underlying normal fibroblasts is inhibited by RGD-containing synthetic peptides. Folia Histochem. Cytobiol. 40 (2002) 251–260.
Madeja, Z., Sroka, J., Nystrom, C., Bjorkhem-Bergman, L., Nordman, T., Damdimopoulos, A., Nalvarte, I., Eriksson, L.C., Spyrou, G., Olsson, J.M. and Bjornstedt, M. The role of thioredoxin reductase activity in selenium-induced cytotoxicity. Biochem. Pharmacol. 69 (2005) 1765–1772.
Sroka, J., Kaminski, R., Michalik, M., Madeja, Z., Przestalski, S. and Korohoda, W. The effect of triethyllead on the motile activity of Walker 256 carcinosarcoma cells. Cell. Mol. Biol. Lett. 9 (2004) 15–30.
Hempstock, J., Kavanagh, J.P. and George, N.J. Growth inhibition of prostate cell lines in vitro by phyto-oestrogens. Br. J. Urol. 82 (1998) 560–563.
Lin, X., Switzer, B.R. and Demark-Wahnefried, W. Effect of mammalian lignans on the growth of prostate cancer cell lines. Anticancer Res. 21 (2001) 3995–3999.
Bhatia, N. and Agarwal, R. Detrimental effect of cancer preventive phytochemicals silymarin, genistein and epigallocatechin 3-gallate on epigenetic events in human prostate carcinoma DU145 cells. Prostate 46 (2001) 98–107.
Papazisis, K.T., Kalemi, T.G., Zambouli, D., Geromichalos, G.D., Lambropoulos, A.F., Kotsis, A., Boutis, L.L. and Kortsaris, A.H. Synergistic effects of protein tyrosine kinase inhibitor genistein with camptothecins against three cell lines in vitro. Cancer Lett. 233 (2006) 255–264.
Pan, W., Ikeda, K., Takebe, M. and Yamori, Y. Genistein, daidzein and glycitein inhibit growth and DNA synthesis of aortic smooth muscle cells from stroke-prone spontaneously hypertensive rats. J. Nutr. 131 (2001) 1154–1158.
Rickard, D.J., Monroe, D.G., Ruesink, T.J., Khosla, S., Riggs, B.L. and Spelsberg, T.C. Phytoestrogen genistein acts as an estrogen agonist on human osteoblastic cells through estrogen receptors alpha and beta. J. Cell Biochem. 89 (2003) 633–646.
Kumi-Diaka, J., Saddler-Shawnette, S., Aller, A. and Brown, J. Potential mechanism of phytochemical-induced apoptosis in human prostate adenocarcinoma cells: Therapeutic synergy in genistein and β-lapachone combination treatment. Cancer Cell Int. 5 (2004) 1–9.
de Lemos, M.L. Effects of soy phytoestrogens genistein and daidzein on breast cancer growth. Ann. Pharmacother. 35 (2001) 1118–1121.
Wietrzyk, J., Opolski, A., Madej, J. and Radzikowski, C. Antitumour and antimetastatic effect of genistein alone or combined with cyclophosphamide in mice transplanted with various tumours depends on the route of tumour transplantation. In Vivo 14 (2000) 357–362.
Magee, P.J., McGlynn, H. and Rowland, I.R. Differential effects of isoflavones and lignans on invasiveness of MDA-MB-231 breast cancer cells in vitro. Cancer Lett. 208 (2004) 35–41.
Alhasan, S.A., Aranha, O. and Sarkar, F.H. Genistein elicits pleiotropic molecular effects on head and neck cancer cells. Clin. Cancer Res. 7 (2001) 4174–4181.
Fotsis, T., Pepper, M., Adlercreutz, H., Fleischmann, G., Hase, T., Montesano, R. and Schweigerer, L. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc. Natl. Acad. Sci. USA 90 (1993) 2690–2694.
Wietrzyk, J., Boratynski, J., Grynkiewicz, G., Ryczynski, A., Radzikowski, C. and Opolski, A. Antiangiogenic and antitumour effects in vivo of genistein applied alone or combined with cyclophosphamide. Anticancer Res. 21 (2001) 3893–3896.
Li, Y. and Sarkar, F.H. Down-regulation of invasion and angiogenesis-related genes identified by cDNA microarray analysis of PC3 prostate cancer cells treated with genistein. Cancer Lett. 186 (2002) 157–164.
Czyz, J., Madeja, Z., Irmer, U., Korohoda, W. and Hulser, D.F. Flavonoid apigenin inhibits motility and invasiveness of carcinoma cells in vitro. Int. J. Cancer 114(1) (2005) 12–18.
Abercrombie, M. Contact inhibition and malignancy. Nature 281 (1979) 259–262.
Adlercreutz, H., Markkanen, H. and Watanabe, S. Plasma concentrations of phyto-oestrogens in Japanese men. Lancet 342 (1993) 1209–1210.
Morton, M.S., Matos-Ferreira, A., Abranches-Monteiro, L., Correia, R., Blacklock, N., Chan, P.S., Cheng, C., Lloyd, S., Chieh-ping, W. and Griffiths, K. Measurement and metabolism of isoflavonoids and lignans in the human male. Cancer Lett. 114 (1997) 145–151.
Simoncini, T., Scorticati, C., Mannella, P., Fadiel, A., Giretti, M.S., Fu, X.D., Baldacci, C., Garibaldi, S., Caruso, A., Fornari, L., Naftolin, F. and Genazzani, A.R. Estrogen receptor alpha interacts with Galpha13 to drive actin remodeling and endothelial cell migration via the RhoA/Rho kinase/moesin pathway. Mol. Endocrinol. 20 (2006) 1756–1771.