Abstract
The isoflavonoids in soy, genistein and daidzein, have been proposed to contribute an important part of the anti-cancer effect of soy. Although there have been many interesting studies on the effects of isoflavones on biochemical targets in tissue culture experiments, in most cases the concentrations used by investigators have exceeded 10 μM. However, based on simple pharmacokinetic calculations involving daily intake of isoflavones, absorption from the gut, distribution to peripheral tissues, and excretion, it is unlikely that blood isoflavone concentrations even in high soy consumers could be greater than 1–5 μM. Experiments designed to evaluate these pharmacological principles were carried out in anesthetized rats with indwelling biliary catheters and in human volunteers consuming soy beverages. The data from these experiments indicate that genistein is efficiently absorbed from the gut, taken up by the liver and excreted in the bile as its 7-O-β-glucuronide. Re-infused genistein 7-O-β-glucuronide was also well absorbed from the gut, although this occurred in the distal small intestine. In human subjects fed a soy beverage for a period of two weeks, plasma levels of genistein and daidzein, determined by HPLC-mass spectrometry, ranged from 0.55–0.86 μM, mostly as glucuronide and sulfate conjugates. In summary, genistein is well absorbed from the small intestine and undergoes an enterohepatic circulation. Although the plasma genistein levels achievable with soy food feeding are unlikely to be sufficient to inhibit the growth of mature, established breast cancer cells by chemotherapeutic-like mechanisms, these levels are sufficient to regulate the proliferation of epithelial cells in the breast and thereby may cause a chemopreventive effect.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Adlercreutz H, H. Honjo, A. Higashi, T. Fotsis, E. Hämäläinen, T. Hasegawa and H. Okada. Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet. Am J Clin Nutr 54: 1093–1100 (1991).
Adlercreutz, H., T. Fotsis, K. Wähälä, T. Mäkelä, and T. Hase. Isotope dilution gas chromatographic-mass spectrometric method for the determination of unconjugated lignans and isoflavonoids in human feces, with preliminary results in omnivorous and vegetarian women. Anal Biochem 225: 101–108 (1995).
Akiyama, T., J. Ishida, S. Nakagawa, H. Ogawara, S. Watanabe, N. M. Itoh, M. Shibuya, and Y. Fukami. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 262: 5592–5595 (1987).
Anderson J. W., B. M. Johnstone, and M. E. Cook-Newell. Meta-analysis of the effects of soy protein intake on serum lipids. New EnglJ Med 333: 276–282 (1995).
Barnes, S., C. Grubbs, K. D. R. Setchell, and J. Carlson. Soybeans inhibit mammary tumors in models of breast cancer, in: “Mutagens and carcinogens in the diet”, ed. M. Pariza, Alan R. Liss, New York, pp. 239–253 (1990).
Barnes, S., M. Kirk, and L. Coward. Isoflavones and their conjugates in soy foods: extraction conditions and analysis by HPLC-mass spectrometry. J Agric Food Chem 42: 2466–2474 (1994).
Barnes, S., M. Kirk, and L. Coward. Isoflavonoids in soy—all is not what it seems, in: “Physiologically functional foods”, A. Caregay, ed., AOCS Press, in press (1995).
Barnes, S., M. Kirk, and L. Coward. Soy isoflavonoids: the key to good health, in: “Hypernutritious foods”, J. W. Finley & D. J. Armstrong, eds., American Chemical Society, Washington, DC, in press (1995).
Barnes, S. and T. G. Peterson. Biochemical targets of the isoflavone genistein in tumor cell lines. Proc Soc Exptl Biol Med 208: 103–108(1995).
Batterham, T. J., N. K. Hart, and J. A. Lamberton. Metabolism of oestrogenic isoflavones in sheep. Nature 206: 509, 1965.
Blair, H. C., S. E. Jordan, T. G. Peterson, and S. Barnes. Variable effect of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats. J Cell Biochem, accepted for publication, 1996.
Booth, A. N., F. T. Jones & F. DeEds. Metabolic fate of hesperidin, eriodictyol, homoeriodictyol, and diosmin. J Biol Chem 230: 661–668 (1958).
Cantley, L. C., K. R. Auger, C. Carpenter, B. Duckworth, R. Kapeller, and S. Soltoff. Oncogenes and signal transduction. Cell 64: 281–302 (1991).
Coward, L., M. Kirk, and S. Barnes. Analysis of Plasma Isoflavones by Reversed-Phase HPLC-Multiple Reaction Ion Monitoring-Mass Spectrometry. Clin Chim Acta, accepted for publication, 1996.
Farmakalidis E. and P. A. Murphy. Isolation of 6”-O-acetyldaidzein and 6”-O-acetylgenistein from toasted defatted soy flakes. J Agric Food Chem 33: 385–389 (1985).
Griffiths, L. A. and G. E. Smith. Metabolism of apigenin and related compounds in the rat. Metabolite formation in vivo and by the intestinal microflora in vitro. Biochem J, 128: 901–911 (1972).
Griffiths, L. A. In: “The Flavonoids: Advances in Research”, J. Harborne & T. J. Mabry, eds, Chapman and Hall London (1982).
Hackett, A. M. The metabolism of flavonoid compounds in mammals, in: “Plant Flavonoids in Biology and Medicine: Biochemical, Pharmacological, and Structure-Activity Relationships”, A. R. Liss, pp 177–194(1986).
Helms J. R. and J. J. Gallaher. The effect of dietary soy protein isolate and genistein on the development of preneoplastic lesions (aberrant crypts) in rats. JNutr 125: 802S (1995).
Kalu, D. N., E. J. Masoro, B. P. Yu, R. R. Hardin, and B. W. Hollis. Modulation of age-related hyperparathyroidism and senile bone loss in Fischer rats by soy protein and food restriction. Endocrinol 122:1847–1854 (1988).
Kao, P. C. and F. K. P’eng. How to reduce the risk factors of osteoporosis in Asia? Chinese Med J 55: 209–213 (1995).
Kelly, G. E., C. Nelson, M. A. Waring, G. E. Joannu, and A. Y. Reeder. Metabolites of dietary (soya) isoflavones in human urine. Clin Chim Acta 223: 9–22, 1993.
Kralli, A., S. P. Bohen, and K. R. Yamamoto. LEM1, an ATP-binding cassette transporter selectively modulates the biological efficacy of steroid hormones. Mol Biol Cell 5: (suppl) 18A (1994).
Kudou, S., Y. Fleury, D. Welti, D. Magnolato, T. Uchida, K. Kitamura, and K. Okubo. Malonyl isoflavone glycosides in soybean seeds (Glycine max MERRILL). Agric Biol Chem 55: 2227–2233, 1991.
Lamartiniere, C. A., J. Moore, M. Holland, and S. Barnes. Genistein and chemoprevention of breast cancer. Proc Soc Exptl Biol Med 208: 120–123 (1995).
Messina, M. and S. Barnes. Workshop report from the Division of Cancer Etiology, National Cancer Institute, National Institutes of Health. The role of soy products in reducing risks of certain cancers. J Natl Cancer Inst 83: 541–546 (1991).
Messina, M., V. Persky, K. D. R. Setchell, and S. Barnes. Soy intake and cancer risk: A review of in vitro and in vivo data. Nutr Cancer 21: 113–131 (1994).
Messina, M. Modern applications for an ancient bean: soybeans and the prevention and treatment of chronic disease. J Nutr 125: 567S–569S (1995).
Pereira, M. A., L. H. Barnes, V. L. Rassman, G. V. Kelloff, and V. E. Steele. Use of azoxymethane-induced foci of aberrant crypts in rat colon to identify potential cancer chemopreventive agents. Carcinogenesis 15: 1049–1054 (1994).
Peterson, T. G. and S. Barnes. Genistein inhibition of the growth of human breast cancer cells: independence from estrogen receptors and the multi-drug resistance gene. Biochem Biophys Res Commun 179, 661–667 (1991).
Peterson, T. P. and S. Barnes. Genistein potently inhibits the growth of human primary breast epithelial cells: correlation with a lack of genistein metabolism. Mol Biol Cell 5: 384a (1994).
Peterson, T. G. Evaluation of the biochemical targets of genistein in tumor cells. J Nutr 125: 784S–789S (1995).
Wang H-J. and P.A. Murphy. Isoflavone content in commercial soybean foods. J Agric Food Chem 42: 1666–1673 (1994).
Wei, H., L. Wei, K. Frankel, R. Bowen, and S. Barnes. Inhibition of tumor promoter-induced hydrogen peroxide formation in vitro and in vivo by genistein. Nutr Cancer 20: 1–12 (1993).
Wei, H., R. Bowen, Q. Cai, S. Barnes, and Y. Wang. Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exptl Biol Med 208: 124–130 (1995).
Weiner, I. M., J. E. Glasser, and L. Lack. Am J Physiol 207: 964–970 (1964).
Xu, X., H-J. Wang, P. A. Murphy, L. Cook, and S. Hendrich. Daidzein is a more bioavailable soymilk isoflavone than is genistein in adult women. J Nutr 124: 825–832 (1994).
Xu, X., K. S. Harris, H. J. Wang, P. A. Murphy & S. Hendrich. Bioavailability of soybean isoflavones depends upon gut microflora in women. J Nutr 125: 2307–2315 (1995).
Yueh T-L. and H-Y. Chu. The metabolic fate of daidzein. Sci Sin 20: 513–521 (1977).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Plenum Press, New York
About this chapter
Cite this chapter
Barnes, S., Sfakianos, J., Coward, L., Kirk, M. (1996). Soy Isoflavonoids and Cancer Prevention. In: Dietary Phytochemicals in Cancer Prevention and Treatment. Advances in Experimental Medicine and Biology, vol 401. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0399-2_7
Download citation
DOI: https://doi.org/10.1007/978-1-4613-0399-2_7
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-8034-4
Online ISBN: 978-1-4613-0399-2
eBook Packages: Springer Book Archive