Antiproliferative activity of daidzein and genistein may be related to ERα/c-erbB-2 expression in human breast cancer cells

Choi,Eun  Jeong; Kim,Gun-Hee

doi:10.3892/mmr.2013.1283

Antiproliferative activity of daidzein and genistein may be related to ERα/c-erbB-2 expression in human breast cancer cells

Authors:
- Eun Jeong Choi
- Gun-Hee Kim
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Affiliations: Plant Resources Research Institute, Duksung Women's University, Seoul 132-714, Republic of Korea
Published online on: January 21, 2013 https://doi.org/10.3892/mmr.2013.1283
Pages: 781-784

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Abstract

In this study, we investigated the antiproliferative activity of the isoflavones daidzein and genistein in three breast cancer cell lines with different patterns of estrogen receptor (ER) and c‑erbB‑2 protein expression (ERα‑positive MCF‑7 cells, c‑erbB‑2‑positive SK‑BR‑3 cells and ERα/c‑erbB‑2‑positive ZR‑75‑1). After treatment at various concentrations (1‑200 µM for 72 h), the effect of daidzein and genistein on the proliferation of different cell types varied; these effects were found to be associated with ERα and c‑erbB‑2 expression. Daidzein and genistein exhibited biphasic effects (stimulatory or inhibitory) on proliferation and ERα expression in MCF‑7 cells. Although 1 µM daidzein significantly stimulated cell growth, ERα expression was unaffected. However, genistein showed marked increases in proliferation and ERα expression after exposure to <10 µM genistein. Notably, the inhibition of cell proliferation by 200 µM genistein was greater compared to that by daidzein at the same concentration. Daidzein and genistein significantly inhibited proliferation of SK‑BR‑3 and ZR‑75‑1 cells in a dose‑dependent manner. In addition, ERα and c‑erbB‑2 expression was reduced by daidzein and genistein in both SK‑BR‑3 and ZR‑75‑1 cells in a dose‑dependent manner. However, the effect of genistein was greater compared to that of daidzein. In conclusion, the isoflavones daidzein and genistein showed anti‑breast cancer activity, which was associated with expression of the ERα and c‑erbB‑2 receptors.

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1	Liggins J, Bluck LJ, Runswick S, et al: Daidzein and genistein contents of vegetables. Br J Nutr. 84:717–725. 2000.PubMed/NCBI
2	Liggins J, Bluck LJ, Runswick S, et al: Daidzein and genistein content of fruits and nuts. J Nutr Biochem. 11:326–331. 2000. View Article : Google Scholar : PubMed/NCBI
3	Iwasaki M, Inoue M, Otani T, et al: Plasma isoflavone level and subsequent risk of breast cancer among Japanese women: a nested case-control study from the Japan Public Health Center-based prospective study group. J Clin Oncol. 26:1677–1683. 2008. View Article : Google Scholar
4	Lampe JW, Nishino Y, Ray RM, et al: Plasma isoflavones and fibrocystic breast conditions and breast cancer among women in Shanghai, China. Cancer Epidem Biomarkers Prev. 16:2579–2586. 2007. View Article : Google Scholar : PubMed/NCBI
5	Lu LJ, Anderson KE, Grady JJ, et al: Decreased ovarian hormones during a soya diet: implications for breast cancer prevention. Cancer Res. 60:4112–4121. 2000.PubMed/NCBI
6	Vissac-Sabatier C, Bignon YJ and Bernard-Gallon DJ: Effects of the phytoestrogens genistein and daidzein on BRCA2 tumor suppressor gene expression in breast cell lines. Nutr Cancer. 45:247–255. 2003. View Article : Google Scholar : PubMed/NCBI
7	de Lemos ML: Effects of soy phytoestrogens genistein and daidzein on breast cancer growth. Ann Pharmacother. 35:1118–1121. 2001.PubMed/NCBI
8	Pugazhendhi D, Watson KA, Mills S, et al: Effect of sulphation on the oestrogen agonist activity of the phytoestrogens genistein and daidzein in MCF-7 human breast cancer cells. J Endocrinol. 197:503–515. 2008. View Article : Google Scholar : PubMed/NCBI
9	Choi EJ and Kim GH: Hepatoprotective effects of daidzein against 7,12-dimetylbenz[a]anthracene-induced oxidative stress in mice. Int J Mol Med. 23:659–664. 2009.PubMed/NCBI
10	Choi EJ and Lee BH: Evidence for genistein mediated cytotoxicity and apoptosis in rat brain. Life Sci. 75:499–509. 2004. View Article : Google Scholar : PubMed/NCBI
11	Choi EJ, Kim T and Lee MS: Pro-apoptotic effect and cytotoxicity of genistein and genistin in human ovarian cancer SK-OV-3 cells. Life Sci. 80:1403–1408. 2007. View Article : Google Scholar : PubMed/NCBI
12	Choi EJ and Kim GH: Daidzein causes cell cycle arrest at the G1 and G2/M phases in human breast cancer MCF-7 and MDA-MB-453 cells. Phytomedicine. 15:683–690. 2008. View Article : Google Scholar : PubMed/NCBI
13	National Breast Cancer Foundation. http://www.nationalbreastcancer.org/about-breast-cancer/breast-cancer-symptoms. Accessed, March 2011
14	National Cancer Institute. SEER Cancer Statistics Review, 1975–2002. http://seer.cancer.gov/csr/1975_2002/. Accessed, March 2005
15	Guo JM, Xiao BX, Liu DH, et al: Biphasic effect of daidzein on cell growth of human colon cancer cells. Food Chem Toxicol. 42:1641–1646. 2004. View Article : Google Scholar : PubMed/NCBI
16	El Touny LH and Banerjee PP: Identification of a biphasic role for genistein in the regulation of prostate cancer growth and metastasis. Cancer Res. 69:3695–3703. 2009.PubMed/NCBI
17	Hsu JT, Hung HC, Chen CJ, et al: Effects of the dietary phytoestrogen biochanin A on cell growth in the mammary carcinoma cell line MCF-7. J Nutr Biochem. 10:510–517. 1999. View Article : Google Scholar : PubMed/NCBI
18	Sirtori CR, Arnoldi A and Johnson SK: Phytoestrogens: end of a tale? Ann Med. 37:423–438. 2005. View Article : Google Scholar : PubMed/NCBI
19	Björnström L and Sjöberg M: Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes. Mol Endocrinol. 19:833–842. 2005.PubMed/NCBI
20	Sperelakis N: Properties of calcium channels in cardiac muscle and vascular smooth muscle. Mol Cell Biochem. 99:97–109. 1990. View Article : Google Scholar : PubMed/NCBI
21	Plaza-Menacho I, Morandi A, Robertson D, Pancholi S, et al: Targeting the receptor tyrosine kinase RET sensitizes breast cancer cells to tamoxifen treatment and reveals a role for RET in endocrine resistance. Oncogene. 29:4648–4657. 2010. View Article : Google Scholar : PubMed/NCBI
22	Slamon DJ, Clark GM, Wong SG, et al: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 235:177–182. 1987. View Article : Google Scholar : PubMed/NCBI
23	Slamon DJ, Godolphin W, Jones LA, et al: Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 244:707–712. 1989. View Article : Google Scholar : PubMed/NCBI
24	Li Y, Bhuiyan M and Sarkar FH: Induction of apoptosis and inhibition of c-erbB-2 in MDA-MB-435 cells by genistein. Int J Oncol. 15:525–533. 1999.PubMed/NCBI
25	Kim EJ, Shin HK and Park JH: Genistein inhibits insulin-like growth factor-I receptor signaling in HT-29 human colon cancer cells: a possible mechanism of the growth inhibitory effect of Genistein. J Med Food. 8:431–438. 2005. View Article : Google Scholar : PubMed/NCBI
26	Yang X, Yang S, McKimmey C, et al: Genistein induces enhanced growth promotion in ER-positive/erbB-2-overexpressing breast cancers by ER-erbB-2 cross talk and p27/kip1 downregulation. Carcinogenesis. 31:695–702. 2010. View Article : Google Scholar : PubMed/NCBI
27	Grimm D, Wehland M, Pietsch J, et al: Drugs interfering with apoptosis in breast cancer. Curr Pharm Des. 17:272–283. 2011. View Article : Google Scholar : PubMed/NCBI
28	Jin FP and Zhang M: Progress of experimental researches on Chinese herbal compounds for inducing tumor cell apoptosis. Chin J Integr Med. 16:565–571. 2010. View Article : Google Scholar : PubMed/NCBI