Cellular uptake of soy-derived phytoestrogens in vitro and in human whole blood
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Laboratory of Pharmacognosy and Phytochemistry, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University-UGent, Gent, Belgium
Laboratory for Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Faculty of Medicine and Health Sciences, Ghent University Hospital, Gent, Belgium
Department of Uro-gynaecology, Ghent University Hospital, Gent, Belgium
Corresponding author
Arne Heyerick   

Laboratory of Pharmacognosy and Phytochemistry, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University-UGent, Harelbekestraat 72, 9000 Gent, Belgium.
J Pre Clin Clin Res. 2008;2(1):64–70
Epidemiological studies comparing typical Western and traditional Eastern lifestyles indicate that dietary intake of soyderived phytoestrogens, including genistein, daidzein, and equol, may have significant health protective effects on hormone-dependent cancers, osteoporosis and cardiovascular diseases. Phytoestrogens have been demonstrated to exert varying effects depending on tissue, endogenous hormone concentrations, and receptor types. Thus, a detailed understanding of the biodistribution and bioavailability of specific phytoestrogens is required in order to predict the subsequent biologic activities. In this study we aimed to investigate the cellular uptake of these soy-derived phytoestrogens in different cell types, including the mammary MCF-7/6 and MDAB-MB 231 cell lines, the ovarian Ishikawa Var-I cell lines and in murine adipocyte clusters. Furthermore, the biodistribution between serum and cell fraction was also investigated in human whole blood. Equol generally shows a higher cellular uptake when compared with genistein and daidzein. Therefore, equol may be more potent with respect to its relative bioactivity, which is corroborated by the observations of specific health effects associated with the equol-producer phenotype.
Cos P, De Bruyne T, Apers S, Berghe DV, Pieters L, Vlietinck AJ: Phytoestrogens: Recent developments. Planta Med 2003, 69, 589-599.
Bolca S, Possemiers S, Herregat A, Huybrechts I, Heyerick A, De Vriese S, Verbruggen M, Depypere H, De Keukeleire D, Bracke M, De Henauw S, Verstraete W, Van de Wiele T: Microbial and dietary factors are associated with the equol producer phenotype in healthy postmenopausal women. J Nutr 2007, 137, 2242-2246.
Huntley AL, Ernst E: Soy for the treatment of perimenopausal symptoms - a systematic review. Maturitas 2004, 47, 1-9.
Messina M, McCaskill-Stevens W, Lampe JW: Addressing the soy and breast cancer relationship: Review, commentary, and workshop proceedings. J Natl Cancer Inst 2006, 98, 1275-1284.
Holzbeierlein JM, McIntosh J, Thrasher JB: The role of soy phytoestrogens in prostate cancer. Curr Opin Urol 2005, 15, 17-22.
Ye YB, Tang XY, Verbruggen MA, Su YX: Soy isofl avones attenuate bone loss in early postmenopausal chinese women – a single-blind randomized, placebo-controlled trial. Eur J Nutr 2006, 45, 327-334.
Clerici C, Setchell KDR, Battezzati PM, Pirro M, Giuliano V, Asciutti S, Castellani D, Nardi E, Sabatin G, Orlandi S, Baldoni M, Morelli O, Mannarino E, Morelli A: Pasta naturally enriched with isofl avone aglycons from soy germ reduces serum lipids and improves markers of cardiovascular risk. J Nutr 2007, 137, 2270-2278.
Pedersen SB, Bruun JM, Hube F, Kristensen K, Hauner H, Richelsen B: Demonstration of estrogen receptor subtypes alpha and beta in human adipose tissue: Infl uences of adipose cell diff erentiation and fat depot localization. Mol Cell Endocrinol 2001, 182, 27-37.
Minh TB, Watanabe M, Tanabe S, Yamada T, Hata J, Watanabe S: Specifi c accumulation and elimination kinetics of tris(4-chlorophenyl) methane, tris(4-chlorophenyl)methanol, and other persistent organochlorines in humans from Japan. Environ Health Perspect 2001, 109, 927-935.
Soule HD, Vazquez J, Long A, Albert S, Brennan M: Human cell line from a pleural eff usion derived from a breast carcinoma. J Natl Cancer Inst 1973, 51, 1409-1416.
Bracke ME, Vanlarebeke NA, Vyncke BM, Mareel MM: Retinoic acid modulates both invasion and plasma-membrane ruffl ing of MCF-7 human mammary-carcinoma cells-invitro. Br J Cancer 1991, 63, 867-872.
Cailleau R, Young R, Olive M, Reeves WJ: Breast tumor-cell lines from pleural eff usions. J Natl Cancer Inst 1974, 53, 661-674.
Reedy S, Powell D, Williams N, Dodson M, Fitzgerald B: Thoughts on the source of tissue on subsequent cell culture success. Methods Cell Sci 2000, 22, 29-32.
Nagel SC, vom Saal FS, Welshons WV: The eff ective free fraction of estradiol and xenoestrogens in human serum measured by whole cell uptake assays: Physiology of delivery modifi es estrogenic activity. Proc Soc Exp Biol Med 1998, 217, 300-309.
Peterson TG, Ji GP, Kirk M, Coward L, Falany CN, Barnes S: Metabolism of the isofl avones genistein and biochanin a in human breast cancer cell lines. Am J Clin Nutr 1998, 68, 1505-1511.
Peterson TG, Coward L, Kirk M, Falany CN, Barnes S: The role of metabolism in mammary epithelial cell growth inhibition by the isofl avones genistein and biochanin a. Carcinogenesis 1996, 17, 1861- 1869.
Adlercreutz H, Mousavi Y, Clark J, Hockerstedt K, Hamalainen E, Wahala K, Makela T, Hase T: Dietary phytoestrogens and cancer – in vitro and in vivo studies. J Steroid Biochem Mol Biol 1992, 41, 331-337.
Johnston SRD, Haynes BP, Smith IE, Jarman M, Sacks NPM, Ebbs SR, Dowsett M: Acquired tamoxifen resistance in human breast-cancer and reduced intra-tumoural drug concentration. Lancet 1993, 342, 1521-1522.
Evans RM, Currie L, Campbell A: The distribution of ascorbic-acid between various cellular-components of blood, in normal individuals, and its relation to the plasma-concentration. Br J Nutr 1982, 47, 473- 482.
Setchell KDR, Brown NM, Desai P, Zimmer-Nechemias L, Wolfe BE, Brashear WT, Kirschner AS, Cassidy A, Heubi JE: Bioavailability of pure isofl avones in healthy humans and analysis of commercial soy isofl avone supplements. J Nutr 2001, 131, 1362-1375.
Yuan JP, Wang JH, Liu X: Metabolism of dietary soy isofl avones to equol by human intestinal microfl ora – implications for health. Molecular Nutrition & Food Research 2007, 51, 765-781.
Wu J, Oka J, Ezaki J, Ohtomo T, Ueno T, Uchiyama S, Toda T, Uehara M, Ishimi Y: Possible role of equol status in the eff ects of isofl avone on bone and fat mass in postmenopausal Japanese women: A double-blind, randomized, controlled trial. Menopause – J North Amer Menopause Soc 2007, 14, 866-874.
Vatanparast H, Chilibeck PD: Does the eff ect of soy phytoestrogens on bone in postmenopausal women depend on the equol-producing phenotype? Nutr Rev 2007, 65, 294-299.
Jackman KA, Woodman OL, Sobey CG: Isofl avones, equol and cardiovascular disease: Pharmacological and therapeutic insights. Curr Med Chem 2007, 14, 2824-2830.
Atkinson C, Frankenfeld CL, Lampe JW: Gut bacterial metabolism of the soy isofl avone daidzein: Exploring the relevance to human health. Exp Biol Med 2005, 230, 155-170.
Setchell KDR, Brown NM, Lydeking-Olsen E: The clinical importance of the metabolite equol – a clue to the eff ectiveness of soy and its isofl avones. J Nutr 2002, 132, 3577-3584.