Hostname: page-component-745bb68f8f-b95js Total loading time: 0 Render date: 2025-01-10T19:37:10.979Z Has data issue: false hasContentIssue false
  • English
  • Français

Growth inhibition of human endothelial cells by the phyto-oestrogen biochanin A, a metabolite of genistein

Published online by Cambridge University Press:  09 March 2007

Chingwen Ying ,
Jih-Tay Hsu  and
Show-Chi Shieh
Chingwen Ying*
Affiliation:
Department of Microbiology, Soochow University, Taipei, Taiwan, Republic of China
Jih-Tay Hsu
Affiliation:
Department of Animal Sciences, National Taiwan University, Taipei, Taiwan, Republic of China
Show-Chi Shieh
Affiliation:
Department of Microbiology, Soochow University, Taipei, Taiwan, Republic of China
*
*Corresponding author: Dr C. Ying, fax +886-2-2883-1193, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

This study examined the growth regulatory effects of a phyto-oestrogen, biochanin A, on a transformed human endothelial cell line ECV304 in vitro. Biochanin A was found to inhibit cell proliferation in a dose-dependent fashion and this effect was influenced by the concentration of serum present in the culture medium. In the absence of serum, the calculated IC50 of biochanin A was 0.18 ± 0.1 μM COMPARED TO AN IC50 OF 35±5 Μm at 10 % serum. At low cell density, the growth inhibitory effects of biochanin A were more evident than at high cell density. Co-administration of a synthetic oestrogen diethylstilboestrol with biochanin A did not suppress the growth regulatory effects of biochanin A treatment. We conclude that biochanin A inhibits the cell proliferation of human endothelial cells at concentrations that are physiologically achievable in vivo and that this effect may play an important role in the cancer-preventing activity of the phyto-oestrogens.

Keywords

Phyto-oestrogenEndothelial cellsCell proliferation
Type
Research Article
Information
British Journal of Nutrition , Volume 85 , Issue 5 , May 2001 , pp. 615 - 620
Copyright
Copyright © The Nutrition Society 2001

References

Adlercreutz, H (1995) Phytoestrogens: epidemiology and a possible role in cancer protection. Environmental Health Perspective 103, 103–112.Google Scholar
Adlercreutz, H, Fotsis, T, Heikkinen, R, Dwyer, JT et al. (1982) Excretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian postmenopausal women and in women with breast cancer. Lancet 2, 1295–1299.CrossRefGoogle ScholarPubMed
Adlercreutz, H, Fotsis, T, Bannwart, C & Wahala, K et al. (1986) Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on habitual diets. Journal of Steroid Biochemistry 25, 791–797.CrossRefGoogle ScholarPubMed
Adlercreutz, CH, Goldin, BR, Gorbach, SL, Hockerstedt, KA, Watanabe, S, Hamalainen, EK, Markkanen, MH, Makela, TH, Whala, KT, Hase, TA & Fotsis, T (1995) Soybean phytoestrogen intake and cancer risk. Journal of Nutrition 125, 757s–770s.Google Scholar
Akiyama, T, Ishida, J, Nakagawa, S, Itoh, N, Shibuya, M & Fukami, Y (1987) Genistein a specific inhibitor of tyrosine-specific protein kinases. Journal of Biological Chemistry 262, 5592–5595.CrossRefGoogle ScholarPubMed
Barnes, S, Grubbs, C, Setchell, KD & Carlson, J (1990) Soybeans inhibit mammary tumors in models of breast cancer. Progression of Clinical Biological Research 347, 239–253.Google Scholar
Blood, CH & Zetter, BR (1990) Tumor interactions with the vasculature: angiogenesis and tumor metastasis. Biochimia Biophysical Acta 1032, 89–118.Google Scholar
Denekamp, J (1990) Vascular attack as a therapeutic strategy for cancer. Cancer Metastasis Review 9, 267–282.CrossRefGoogle ScholarPubMed
Eldridge, A & Kwolek, WF (1983) Soybean isoflavones: effect of environment and variety on composition. Journal of Agriculture and Food Chemistry 31, 394–396.Google Scholar
Folkman, J (1985) Tumor angiogenesis. Advanced Cancer Research 43, 175–203.Google Scholar
Folkman, J & Cotran, RS (1976) Relation of vascular proliferation to tumor growth. International Review of Experimental Pathology 16, 207–248.Google Scholar
Folkman, J, Walson, K, Ingber, D & Hanahan, D (1989) Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 339, 58–61.Google Scholar
Fotsis, T, Pepper, M, Adlercreutz, H, Fleischmann, G, Hase, T, Montesano, R & Schweigerer, L (1993) Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proceedings of National Academic Science USA 90, 2690–2694.Google Scholar
Fotsis, T, Pepper, MS, Aktas, E, Breit, S, Rasku, S, Adlercreutz, H, Wahala, K, Montesano, R & Schweigerer, L (1997) Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis. Cancer Research 57, 2916–2921.Google ScholarPubMed
Hawrylewicz, EJ, Zapata, JJ & Blair, BH (1995) Soy and experimental cancer: animal studies. Journal of Nutrition 125, 698s–708s.Google ScholarPubMed
Hempstock, J, Kavanagh, JP & George, NJR (1998) Growth inhibition of prostate cell lines in vitro by phyto-oestrogens. British Journal of Urology 82, 560–563.Google Scholar
Herman, C, Adlercreutz, T, Goldin, BR, Gorbach, SL, Hockerstedt, KAV, Watansbe, S, Hamalainen, EK, Markkanen, MH, Makela, TH, Wahala, KT, Hase, AT & Fotsis, T (1995) Soybean phytoestrogen intake and cancer risk. American Institute of Nutrition 125, 757s–770s.Google Scholar
Honma, Y, Okabe-Kado, J, Kasukabe, T, Hozumi, M & Umezawa, K (1990) Inhibition of ubl oncogenic tyrosine kinase induces erythroid differentiation of human myelogenous leukemia K562 cells. Journal of Cancer Research 81, 1132–1136.Google Scholar
Hsu, J, Hung, H, Chen, C, Hsu, W & Ying, C (1999) Effects of the dietary phytoestrogen biochanin A on cell growth in the mammary carcinoma cell line MCF-7. Journal of Nutritional Biochemistry 10, 510–517.CrossRefGoogle ScholarPubMed
Klagsbrun, M, Folkman, J (1990) In Peptide Growth Factors and Their Receptors II. 549–586.[Sporn, MB, Roberts, AB, editors]. Berlin: Springer-Verlag.CrossRefGoogle Scholar
Kolonel, LN (1988) Variability in diet and its relation to risk in ethnic and migrant groups. Basic Life Science 43, 129–135.Google ScholarPubMed
Kurzer, MS & Xu, X (1997) Dietary phytoestrogens. Annual Review of Nutrition 17, 353–381.Google Scholar
Lee, HP, Courley, L & Duffy, SW (1991) Dietary effects on breast cancer risk in Singapore. Lancet 337, 1197–1200.Google Scholar
Liotta, LA, Steeg, PS & Stetler-Stevenson, WC (1991) Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation. Cell 64, 327–336.Google Scholar
Lyn-Cook, BD, Stottman, HL, Yan, Y, Blann, E, Kadlubar, FF & Hammons, GJ (1999) The effects of phytoestrogen on human pancreatic tumor cells in vitro. Cancer Letters 142, 111–119.Google Scholar
Makela, S, Davis, VL, Tally, WC, Korkman, J & Salo, L et al. (1994) Dietary estrogen acts through estrogen receptor-mediated processes and shows no antiestrogen in cultured breast cancer cells. Environmental Health Perspective 102, 572–578.CrossRefGoogle Scholar
Matsukawa, Y, Marui, N, Sakai, T, Satomi, Y, Yoshida, K, Matsumoto, K, Nishino, H & Aoike, A (1993) Genistein arrests cell cycle progression at G(2)-M. Cancer Research 53, 1328–1331.Google Scholar
McIntosh, GH, Regester, GO, Le Leu, RK, Royle, PJ & Smithers, GW (1995) Dairy proteins protect against dimethylhydrazine-induced intestinal cancers in rats. Journal of Nutrition 125, 809–816.Google ScholarPubMed
Naim, M, Geststner, B, Bondi, A & Birk, Y (1976) Antioxidative and antihemolytic activities of soybean isoflavone. Journal of Agriculture and Food Chemistry 24, 1174–1177.Google Scholar
Okura, A, Arakawa, H, Oka, H, Yoshinari, T & Monden, Y (1988) Effect of genistein on topoisomerase activity and on the growth of [VAL12]Ha-ras-transformed NIH 3T3 cells. Biochemistry and Biophysics Research Communication 157, 183–189.CrossRefGoogle ScholarPubMed
Peterson, G (1995) Evaluation of the biochemical targets of genistein in tumor cells. Journal of Nutrition 125, 784s–789s.Google Scholar
Rao, CV, Wang, C-X, Simi, B, Lubet, R, Kelloff, G, Steele, V & Reddy, BS (1997) Enhancement of experimental colon cancer by genistein. Cancer Research 57, 3717–3722.Google ScholarPubMed
Rose, DP, Boyar, AP & Wynder, EL (1986) International comparison of mortality rates for cancer of the breast, ovary, prostate, and per capita food consumption. Cancer 58, 2363–2371.3.0.CO;2-#>CrossRefGoogle ScholarPubMed
SAS, (1990). SAS/STAT® User's Guide (Release 6.04) Vol. 2, SAS Inst. Inc., Cary, NC, USA.Google Scholar
Setchell, KDR, Adlercreutz, H (1988) Mammalian lignans and phytoestrogens. Recent studies on their formation, metabolism and biological role in health and disease In Role of the Gut Flora in Toxicity and Cancer 315–345.[Rowland, I, editor].London: Academic Press.CrossRefGoogle Scholar
Snedecor, GW & Cochran, WG (1980) Statistical Methods. 7th ed. Ames, IA: Iowa State University Press.Google Scholar
Shutt, DA & Cox, RI (1972) Steroid and phytoestrogen binding to sheep uterine receptors in vitro. Endocrinology 52, 299–310.Google Scholar
Trowell, HC & Burkitt, DP (1981) Western Diseases: Their Emergence and Prevention. London: Edward Arnold Ltd.Google Scholar
Wang, C & Kurzer, MS (1998) Effects of phytoestrogen on DNA synthesis in MCF-7 cells in the presence of estradiol or growth factors. Nutrition and Cancer 31, 90–100.CrossRefGoogle ScholarPubMed
Xu, X, Wang, H-J, Murphy, PA, Cook, L & Hendrich, S (1994) Daidzein is a more bioavailable soymilk isoflavone than is genistein in adult women. Journal of Nutrition 124, 825–832.CrossRefGoogle ScholarPubMed
Zhou, JR, Gugger, ET, Tanaka, T, Guo, Y, Blackburn, GL & Clinton, SK (1999) Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice. Journal of Nutrition 129, 1628–1635.CrossRefGoogle ScholarPubMed
Zava, DT & Duwe, G (1997) Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro. Nutrition and Cancer 27, 31–40.CrossRefGoogle ScholarPubMed