Skip to main content
SpringerLink
Log in

Membrane Fluidity, Invasiveness and Dynamic Phenotype of Metastatic Prostate Cancer Cells after Treatment with Soy Isoflavones

  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

Abstract

Soy isoflavones represent hopeful unconventional remedies in the therapy of prostate cancer. The aim of our study was to determine the effects of genistein and daidzein on the parameters that reflect metastatic potential, membrane fluidity, invasiveness and dynamic phenotype in Matrigel of LNCaP and PC-3 prostate cancer cells. Cell viability tests, using a wide range of concentrations of soy isoflavones (6–75 μg/ml for 72 h), were conducted to determine their IC50 concentrations. Electron paramagnetic resonance investigations of prostate cancer cell membrane fluidity were performed at IC50 concentrations of genistein and daidzein (12.5 and 25 μg/ml, respectively, for 10 min). Genistein provoked significant increases in the membrane order parameter (which is reciprocally proportional to membrane fluidity) of 0.722 ± 0.006 (LNCaP), 0.753 ± 0.010 (LNCaP + genistein), 0.723 ± 0.007 (PC-3) and 0.741 ± 0.004 (PC-3 + genistein); however, no such effects were observed for daidzein. While both genistein and daidzein reduced the proliferation of prostate cancer cells at their respective IC50 concentrations, during the 72 h of incubation only genistein provoked effects on the dynamic phenotype and decreased invasiveness. The effect was more evident in PC-3 cells compared to LNCaP cells. Our results imply that (1) invasive activity is at least partially dependent on membrane fluidity, (2) genistein may exert its antimetastatic effects by changing the mechanical properties of prostate cancer cells and (3) daidzein should be applied at higher concentrations than genistein in order to achieve pharmacological effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Aalinkeel R, Nair MP, Sufrin G, Mahajan SD, Chadha KC, Chawda RP, Schwartz SA (2004) Gene expression of angiogenic factors correlates with metastatic potential of prostate cancer cells. Cancer Res 64:5311–5321

    Article  PubMed  CAS  Google Scholar 

  • Ajdžanović V, Spasojević I, Filipović B, Šošić-Jurjević B, Sekulić M, Milošević V (2010) Effects of genistein and daidzein on erythrocyte membrane fluidity: an electron paramagnetic resonance study. Can J Physiol Pharmacol 88:497–500

    Article  PubMed  Google Scholar 

  • Ajdžanović V, Spasojević I, Šošić-Jurjević B, Filipović B, Trifunović S, Sekulić M, Milošević V (2011) The negative effect of soy extract on erythrocyte membrane fluidity: an electron paramagnetic resonance study. J Membr Biol 239:131–135

    Article  PubMed  Google Scholar 

  • Ajdžanović V, Spasojević I, Pantelić J, Šošić-Jurjević B, Filipović B, Milošević V, Severs W (2012) Vitex agnus-castus L. essential oil increases human erythrocyte membrane fluidity. J Med Biochem 31:222–227

    Article  Google Scholar 

  • Albertsen PC, Hanley JA, Fine J (2005) 20-Year outcomes following conservative management of clinically localized prostate cancer. JAMA 293:2095–2101

    Article  PubMed  CAS  Google Scholar 

  • Bergan R, Kyle E, Nguyen P, Trepel J, Ingui C, Neckers L (1996) Genistein-stimulated adherence of prostate cancer cells is associated with the binding of focal adhesion kinase to beta-1-integrin. Clin Exp Metastasis 14:389–398

    Article  PubMed  CAS  Google Scholar 

  • Birt DF, Hendrich S, Wang W (2001) Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacol Ther 90:157–177

    Article  PubMed  CAS  Google Scholar 

  • Chang KL, Cheng HL, Huang LW, Hsieh BS, Hu YC, Chih TT, Shyu HW, Su SJ (2009) Combined effects of terazosin and genistein on a metastatic, hormone-independent human prostate cancer cell line. Cancer Lett 276:14–20

    Article  PubMed  CAS  Google Scholar 

  • Deliconstantinos G (1987) Physiological aspects of membrane lipid fluidity in malignancy. Anticancer Res 7:1011–1021

    PubMed  CAS  Google Scholar 

  • Gonda K, Watanabe TM, Ohuchi N, Higuchi H (2010) In vivo nano-imaging of membrane dynamics in metastatic tumor cells using quantum dots. J Biol Chem 285:2750–2757

    Article  PubMed  CAS  Google Scholar 

  • Guarino M, Rubino B, Ballabio G (2007) The role of epithelial–mesenchymal transition in cancer pathology. Pathology 39:305–318

    Article  PubMed  CAS  Google Scholar 

  • Heinlein CA, Chang C (2004) Androgen receptor in prostate cancer. Endocr Rev 25:276–308

    Article  PubMed  CAS  Google Scholar 

  • Huang X, Chen S, Xu L, Liu Y, Deb DK, Platanias LC, Bergan RC (2005) Genistein inhibits p38 map kinase activation, matrix metalloproteinase type 2, and cell invasion in human prostate epithelial cells. Cancer Res 65:3470–3478

    PubMed  CAS  Google Scholar 

  • Hwang YW, Kim SY, Jee SH, Kim YN, Nam CM (2009) Soy food consumption and risk of prostate cancer: a meta-analysis of observational studies. Nutr Cancer 61:598–606

    Article  PubMed  CAS  Google Scholar 

  • Jefferson WN, Padilla-Banks E, Newbold RR (2007) Disruption of the female reproductive system by the phytoestrogen genistein. Rep Tox 23:308–316

    Article  CAS  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  • Kampa M, Papakonstanti EA, Hatzoglou A, Stathopoulos EN, Stournaras C, Castanas E (2002) The human prostate cancer cell line LNCaP bears functional membrane testosterone receptors, which increase PSA secretion and modify actin cytoskeleton. FASEB J 16:1429–1431

    PubMed  CAS  Google Scholar 

  • Kido J, Ashida Y, Shinkai K, Akedo H, Isoai A, Kumagai H, Inoue H (1991) Effects of methylthiodeoxyadenosine and its analogs on in vitro invasion of rat ascites hepatoma cells and methylation of their phospholipids. Jpn J Cancer Res 82:1104–1111

    Article  PubMed  CAS  Google Scholar 

  • Krubasik D, Iyer NG, English WR, Ahmed AA, Vias M, Roskelley C, Brenton JD, Caldas C, Murphy G (2006) Absence of p300 induces cellular phenotypic changes characteristic of epithelial to mesenchyme transition. Br J Cancer 94:1326–1332

    Article  PubMed  CAS  Google Scholar 

  • Kuzdzal M, Wesolowska O, Strancar J, Michalak K (2011) Fluorescence and ESR spectroscopy studies on the interaction of isoflavone genistein with biological and model membranes. Chem Phys Lipids 164:283–291

    Article  PubMed  CAS  Google Scholar 

  • Lee MM, Gomez SL, Chang JS, Wey M, Wang RT, Hsing AW (2003) Soy and isoflavone consumption in relation to prostate cancer risk in China. Cancer Epidemiol Biomarkers Prev 12:665–668

    PubMed  CAS  Google Scholar 

  • Li Y, Kucuk O, Hussain M, Abrams J, Cher ML, Sarkar FH (2006) Antitumor and antimetastatic activities of docetaxel are enhanced by genistein through regulation of osteoprotegerin/receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/MMP-9 signaling in prostate cancer. Cancer Res 66:4816–4825

    Article  PubMed  CAS  Google Scholar 

  • Maksimovic-Ivanic D, Mijatovic S, Miljkovic Dj, Harhaji-Trajkovic Lj, Timotijevic G, Mojic M, Dabideen D, Cheng KF, McCubrey JA, Mangano K, Al-Abed Y, Libra M, Garotta G, Stosic-Grujicic S, Nicoletti F (2009) The antitumor properties of a nontoxic, nitric oxide-modified version of saquinavir are independent of Akt. Mol Cancer Ther 8:1169–1178

    Article  PubMed  CAS  Google Scholar 

  • Maxfield FR, Tabas I (2005) Role of cholesterol and lipid organization in disease. Nature 438:612–621

    Article  PubMed  CAS  Google Scholar 

  • McDonnel AC, Van Kirk EA, Isaak DD, Murdoch WJ (2003) Inhibitory effects of progesterone on plasma membrane fluidity and tumorigenic potential of ovarian epithelial cancer cells. Exp Biol Med (Maywood) 228:308–314

    CAS  Google Scholar 

  • Mijatovic S, Maksimovic-Ivanic D, Radovic J, Miljkovic DJ, Harhaji LJ, Vuckovic O, Stosic-Grujicic S, Mostarica Stojkovic M, Trajkovic V (2005) Anti-glioma action of aloe emodin: the role of ERK inhibition. Cell Mol Life Sci 62:589–598

    Article  PubMed  CAS  Google Scholar 

  • Mojic M, Mijatovic S, Maksimovic-Ivanic D, Miljkovic D, Stosic-Grujicic S, Stankovic M, Mangano K, Travali S, Donia M, Fagone P, Zocca MB, Al-Abed Y, McCubrey JA, Nicoletti F (2012) Therapeutic potential of nitric oxide-modified drugs in colon cancer cells. Mol Pharmacol 82:700–710

    Article  PubMed  CAS  Google Scholar 

  • Oh HY, Leem J, Yoon SJ, Yoon S, Hong SJ (2010) Lipid raft cholesterol and genistein inhibit the cell viability of prostate cancer cells via the partial contribution of EGFR-Akt/p70S6k pathway and down-regulation of androgen receptor. Biochem Biophys Res Commun 393:319–324

    Article  PubMed  CAS  Google Scholar 

  • Sahai E (2007) Illuminating the metastatic process. Nat Rev Cancer 7:737–749

    Article  PubMed  CAS  Google Scholar 

  • Scott IC, Stainier DY (2003) Developmental biology: twisting the body into shape. Nature 425:461–463

    Article  PubMed  CAS  Google Scholar 

  • Sherbet GV (1989) Membrane fluidity and cancer metastasis. Exp Cell Biol 57:198–205

    PubMed  CAS  Google Scholar 

  • Singh-Gupta V, Zhang H, Yunker CK, Ahmad Z, Zwier D, Sarkar FH, Hillman GG (2010) Daidzein effect on hormone refractory prostate cancer in vitro and in vivo compared to genistein and soy extract: potentiation of radiotherapy. Pharm Res 27:1115–1127

    Article  PubMed  CAS  Google Scholar 

  • Stacewicz-Sapuntzakis M, Borthakur G, Burns JL, Bowen PE (2008) Correlations of dietary patterns with prostate health. Mol Nutr Food Res 52:114–130

    Article  PubMed  CAS  Google Scholar 

  • Swaminathan V, Mythreye K, O’Brien ET, Berchuck A, Blobe GC, Superfine R (2011) Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines. Cancer Res 71:5075–5080

    Article  PubMed  CAS  Google Scholar 

  • Taylor CK, Levy RM, Elliot JC, Burnett BP (2009) The effect of genistein aglycone on cancer and cancer risk: a review of in vitro, preclinical, and clinical studies. Nutr Rev 67:398–415

    Article  PubMed  Google Scholar 

  • Tsuchiya H, Nagayama M, Tanaka T, Furusawa M, Kashimata M, Takeuchi H (2002) Membrane-rigidifying effects of anti-cancer dietary factors. Biofactors 16:45–56

    Article  PubMed  CAS  Google Scholar 

  • Upadhyay J, Shekarriz B, Nemeth JA, Dong Z, Cummings GD, Fridman R, Sakr W, Grignon DJ, Cher ML (1999) Membrane type 1-matrix metalloproteinase (MT1-MMP) and MMP-2 immunolocalization in human prostate: change in cellular localization associated with high-grade prostatic intraepithelial neoplasia. Clin Cancer Res 5:4105–4110

    PubMed  CAS  Google Scholar 

  • Xu L, Ding Y, Catalona WJ, Yang XJ, Anderson WF, Jovanovic B, Wellman K, Killmer J, Huang X, Scheidt KA, Montgomery RB, Bergan RC (2009) MEK4 function, genistein treatment, and invasion of human prostate cancer cells. J Natl Cancer Inst 101:1141–1155

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi H, Lorenz M, Kempiak S, Sarmiento C, Coniglio C, Symons M, Segall J, Eddy R, Miki H, Takenawa T, Condeelis J (2005) Molecular mechanisms of invadopodia formation: the role of the N-WASP-Arp2/3 complex and cofilin. J Cell Biol 168:441–452

    Article  PubMed  CAS  Google Scholar 

  • Zeisig R, Koklic T, Wiesner B, Fichtner I, Sentjurc M (2007) Increase in the fluidity in the membrane of MT3 breast cancer cells correlates with enhanced cell adhesion in vitro and increased lung metastasis in NOD/SCID mice. Arch Biochem Biophys 459:98–106

    Article  PubMed  CAS  Google Scholar 

  • Zicha J, Kunes J, Devynck MA (1999) Abnormalities of membrane function and lipid metabolism in hypertension. Am J Hypertens 12:315–331

    Article  PubMed  CAS  Google Scholar 

  • Zimmerberg J, Kozlov MM (2006) How proteins produce cellular membrane curvature. Nat Rev Mol Cell Biol 7:9–19

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Ministry of Science, Education and Technological Development of the Republic of Serbia, grant numbers 173009, 173013 and 173014. We owe thanks to Dr. Đorđe Miljković, Institute for Biological Research “Siniša Stanković,” for his help in the cytofluorimetric analysis.

Conflicts of Interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Cytology, Institute for Biological Research “Siniša Stanković,” University of Belgrade, Despot Stefan Blvd. 142, 11060, Belgrade, Serbia

    Vladimir Ajdžanović & Verica Milošević

  2. Department of Immunology, Institute for Biological Research “Siniša Stanković,” University of Belgrade, Despot Stefan Blvd. 142, 11060, Belgrade, Serbia

    Marija Mojić, Danijela Maksimović-Ivanić, Mirna Bulatović & Sanja Mijatović

  3. Department of Life Systems, Institute for Multidisciplinary Research, University of Belgrade, Kneza Višeslava 1, 11000, Belgrade, Serbia

    Ivan Spasojević

Authors
  1. Vladimir Ajdžanović
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marija Mojić
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Danijela Maksimović-Ivanić
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mirna Bulatović
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sanja Mijatović
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Verica Milošević
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ivan Spasojević
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vladimir Ajdžanović.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ajdžanović, V., Mojić, M., Maksimović-Ivanić, D. et al. Membrane Fluidity, Invasiveness and Dynamic Phenotype of Metastatic Prostate Cancer Cells after Treatment with Soy Isoflavones. J Membrane Biol 246, 307–314 (2013). https://doi.org/10.1007/s00232-013-9531-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00232-013-9531-1

Keywords

Search

Navigation