Skip to main content
Log in

Soy-derived Isoflavones Inhibit HeLa Cell Growth by Inducing Apoptosis

  • ORIGINAL PAPER
  • Published:
Plant Foods for Human Nutrition Aims and scope Submit manuscript

Abstract

Isoflavones are among the major bioactive compounds found in a wide variety of plant-derived foods, especially in soybeans and soy-based foods. In this study, the effect of a soy-derived isoflavone mixture (designated as SI-I, containing 71% daidzein, 14.3% genistein and 14.7% glycitein) on HeLa cells and its mechanism were investigated. SI-I in concentration range 5–80 μg/ml significantly reduced the survival rate of HeLa cells by MTT assay, whereas showed no side effect on that of L929 cells. After HeLa cells were exposed to 10, 20 and 40 μg/ml SI-I for 4 days, typical apoptotic morphological changes, including nuclear fragmentation, cytoplasm shrinkage and decrease of cell volume, were observed by fluorescence microscope and CLSM, respectively. FCM analysis revealed that the percentages of early apoptotic cells with lost Δψm increased by 2.27, 2.74 and 4.05 folds respectively, compared with control. The results showed that SI-I inhibited HeLa cell growth through inducing apoptosis via the mitochondrial pathway and comparisons with reported data indicated that synergistic effect existed between the isoflavone species contained in SI-I. It is proposed that natural soy-derived isoflavones are potential candidates as chemoterapeutic agents against human cervical cancer.

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

Access this article

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
Fig. 5

Similar content being viewed by others

Abbreviations

CLSM:

Confocal laser scanning microscope

FCM:

Flow cytometry

FCS:

Fetal calf serum

MTT:

3-(4 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide

Δψm:

Mitochondrial transmembrane potential

References

  1. Zhu D, Hettiarachchy NS, Horax R, Chen P (2005) Isoflavone contents in germinated soybean seeds. Plant Foods Hum Nutr 60(3):147–151

    Article  CAS  Google Scholar 

  2. Genovese MI, Barbosa AC, Pinto Mda S, Lajolo FM (2007) Commercial soy protein ingredients as isoflavone sources for functional foods. Plant Foods Hum Nutr 62(2):53–58

    Article  CAS  Google Scholar 

  3. Su SJ, Yeh TM, Chuang WJ, Ho CL, Chang KL, Cheng HL, Liu HS, Cheng HL, Hsu PY, Chow NH (2005) The novel targets for anti-angiogenesis of genistein on human cancer cells. Biochem Pharmacol 69(2):307–318

    Article  CAS  Google Scholar 

  4. Banerjee S, Li Y, Wang Z, Sarkar FH (2008) Multi-targeted therapy of cancer by genistein. Cancer Lett 269(2):226–242

    Article  CAS  Google Scholar 

  5. Li M, Zhang Z, Hill DL, Chen X, Wang H, Zhang R (2005) Genistein, a dietary isoflavone, down-regulates the MDM2 oncogene at both transcriptional and posttranslational levels. Cancer Res 65(18):8200–8208

    Article  CAS  Google Scholar 

  6. 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(1):14–20

    Article  CAS  Google Scholar 

  7. Khan N, Adhami V, Mukhtar H (2009) Apoptosis by dietary agents for prevention and treatment of prostate cancer. Endocr Relat Cancer 17(1):R39–52

    Article  Google Scholar 

  8. Lin YJ, Hou YC, Lin CH, Hsu YA, Sheu JJ, Lai CH, Chen BH, Lee Chao PD, Wan L, Tsai FJ (2009) Puerariae radix isoflavones and their metabolites inhibit growth and induce apoptosis in breast cancer cells. Biochem Biophys Res Commun 378(4):683–688

    Article  CAS  Google Scholar 

  9. Vantyghem SA, Wilson SM, Postenka CO, Al-Katib W, Tuck AB, Chambers AF (2005) Dietary genistein reduces metastasis in a postsurgical orthotopic breast cancer model. Cancer Res 65(8):3396–3403

    CAS  Google Scholar 

  10. Wang Z, Desmoulin S, Banerjee S, Kong D, Li Y, Deraniyagala RL, Abbruzzese J, Sarkar FH (2008) Synergistic effects of multiple natural products in pancreatic cancer cells. Life Sci 83(7–8):293–300

    Article  CAS  Google Scholar 

  11. Yashar CM, Spanos WJ, Taylor DD, Gercel-Taylor C (2005) Potentiation of the radiation effect with genistein in cervical cancer cells. Gynecol Oncol 99(1):199–205

    Article  CAS  Google Scholar 

  12. Choi EJ, Kim GH (2008) Daidzein causes cell cycle arrest at the G1 and G2/M phases in human breast cancer MCF-7 and MDA-MB-453 cells. Phytomedicine 15(9):683–690

    Article  CAS  Google Scholar 

  13. Jin S, Zhang QY, Kang XM, Wang JX, Zhao WH (2010) Daidzein induces MCF-7 breast cancer cell apoptosis via the mitochondrial pathway. Ann Oncol 21(2):263–268

    Article  CAS  Google Scholar 

  14. Yeh TC, Chiang PC, Li TK, Hsu JL, Lin CJ, Wang SW, Peng CY, Guh JH (2007) Genistein induces apoptosis in human hepatocellular carcinomas via interaction of endoplasmic reticulum stress and mitochondrial insult. Biochem Pharmacol 73(6):782–792

    Article  CAS  Google Scholar 

  15. Ravindranath MH, Muthugounder S, Presser N, Viswanathan S (2004) Anticancer therapeutic potential of soy isoflavone, genistein. Adv Exp Med Biol 546:121–165

    Google Scholar 

  16. Guo JM, Xiao BX, Liu DH, Grant M, Zhang S, Lai YF, Guo YB, Liu Q (2004) Biphasic effect of daidzein on cell growth of human colon cancer cells. Food Chem Toxicol 42(10):1641–1646

    Article  CAS  Google Scholar 

  17. Moore AB, Castro L, Yu L, Zheng X, Di X, Sifre MI, Kissling GE, Newbold RR, Bortner CD, Dixon D (2007) Stimulatory and inhibitory effects of genistein on human uterine leiomyoma cell proliferation are influenced by the concentration. Hum Reprod 22(10):2623–2631

    Article  CAS  Google Scholar 

  18. Guo JM, Kang GZ, Xiao BX, Liu DH, Zhang S (2004) Effect of daidzein on cell growth, cell cycle, and telomerase activity of human cervical cancer in vitro. Int J Gynecol Cancer 14(5):882–888

    Article  CAS  Google Scholar 

  19. Zhou N, Yan Y, Li W, Wang Y, Zheng L, Han S, Yan Y, Li Y (2009) Genistein inhibition of topoisomerase IIα expression participated by Sp1 and Sp3 in HeLa cell. Int J Mol Sci 10(7):3255–3268

    Article  CAS  Google Scholar 

  20. Jamadar-Shroff V, Papich MG, Suter SE (2009) Soy-derived isoflavones inhibit the growth of canine lymphoid cell lines. Clin Cancer Res 15(4):1269–1276

    Article  CAS  Google Scholar 

  21. Zhang B, Liu JY, Pan JS, Han SP, Yin XX, Wang B, Hu G (2006) Combined treatment of ionizing radiation with genistein on cervical cancer HeLa cells. J Pharmacol Sci 102(1):129–135

    Article  CAS  Google Scholar 

  22. Choi EJ, Lee BH (2004) Evidence for genistein mediated cytotoxicity and apoptosis in rat brain. Life Sci 75(4):499–509

    Article  CAS  Google Scholar 

  23. Hirsch T, Marzo I, Kroemer G (1997) Role of the Mitochondrial Permeability Transition Pore in Apoptosis. Biosci Rep 17(1):67–76

    Article  CAS  Google Scholar 

  24. Iannolo G, Conticello C, Memeo L, De Maria R (2008) Apoptosis in normal and cancer stem cells. Crit Rev Oncol Hematol 66(1):42–51

    Article  Google Scholar 

  25. Gustafsson AB, Gottlieb RA (2007) Bcl-2 family members and apoptosis, taken to heart. Am J Physiol Cell Physiol 292(1):C45–51

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the High-Level Talent Scientific Research Foundation of Qingdao Agricultural University (No. 630630).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jun-Xia Xiao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xiao, JX., Huang, GQ., Geng, X. et al. Soy-derived Isoflavones Inhibit HeLa Cell Growth by Inducing Apoptosis. Plant Foods Hum Nutr 66, 122–128 (2011). https://doi.org/10.1007/s11130-011-0224-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11130-011-0224-6

Keywords

Navigation