Plant isoflavones as anticancer agents in nanomedicine

Document Type : Review paper

Authors
Ali Yousefian
Fatemeh Moradian
Department of Basic Sciences, Sari Agricultural Sciences and Natural Resources University, Mazandaran, Iran
10.22058/jpmb.2025.2049548.1326
Abstract
Isoflavones are natural phytoestrogens and belong to a subgroup of flavonoids that can be found mainly in legume plants, especially soybeans (Glycine max L.) and the other plants of the Fabaceae family. They have a structure similar to 17β-estradiol, which allows them to bind estrogen receptors and exhibit estrogenic or antiestrogenic effects. They are found in non-fermented products mainly as glycosides. During the fermentation process, they are converted into bioactive aglycones. Isoflavones are also linked to antioxidant and therapeutic benefits, supporting bone health and cholesterol regulation. Soybean-derived isoflavones, especially genistein, show strong anticancer potential by inhibiting cell growth. Epidemiological studies indicate, that consumption of isoflavones may reduce the risk of some diseases, including breast cancer but these compounds' clinical application is limited due to poor bioavailability, solubility, and stability. Today, integrating traditional medicine and medicinal plants with modern medicine could offer new opportunities for treating various diseases. Nanocarriers such as liposomes, dendrimers, and nanoparticles have been developed to enhance the bioavailability and controlled release of soy isoflavones, enabling their targeted delivery to cancer cells while minimizing off-target effects. In this review, we examine how nanotechnology synergizes with Glycine max-derived isoflavones to enhance their bioavailability and biological activity, considering the challenges and limitations of this approach for therapeutic development.
Keywords
phytoestrogens
Nanotechnology
Cancer
Genistein
Subjects
Ahmad, A., Biersack, B., Li, Y., Kong, D., Bao, B., Schobert, R., B. Padhye, S., and H. Sarkar, F. (2013). Deregulation of PI3K/Akt/mTOR signaling pathways by isoflavones and its implication in cancer treatment. Anti-Cancer Agents Med. Chem. 13(7): 1014-1024.
Amawi, H., Ashby, C.R., and Tiwari, A.K. (2017). Cancer chemoprevention through dietary flavonoids: what’s limiting? Chin. J. Cancer 36: 1-13.
Andreani, T., Cheng, R., Elbadri, K., Ferro, C., Menezes, T., Dos Santos, M.R., Pereira, C.M., and Santos, H.A. (2024). Natural compounds-based nanomedicines for cancer treatment: Future directions and challenges. Drug Deliv Transl Res 14(10): 2845-2916.
Baglia, M.L., Zheng, W., Li, H., Yang, G., Gao, J., Gao, Y.T., and Shu, X.O. (2016). The association of soy food consumption with the risk of subtype of breast cancers defined by hormone receptor and HER2 status. Int J Cancer 139(4): 742-748.
Barańska, A., Kanadys, W., Bogdan, M., Stępień, E., Barczyński, B., Kłak, A., Augustynowicz, A., Szajnik, M., and Religioni, U. (2022). The role of soy isoflavones in the prevention of bone loss in postmenopausal women: A systematic review with meta-analysis of randomized controlled trials. J. Clin. Med. 11(16): 4676.
Barnard, N.D., Kahleova, H., Holtz, D.N., Del Aguila, F., Neola, M., Crosby, L.M., and Holubkov, R. (2021). The Women's Study for the Alleviation of Vasomotor Symptoms (WAVS): a randomized, controlled trial of a plant-based diet and whole soybeans for postmenopausal women. Menopause 28(10): 1150-1156. doi: 10.1097/gme.0000000000001812.
Blicharski, T., and Oniszczuk, A. (2017). Extraction methods for the isolation of isoflavonoids from plant material. Open Chem. 15(1): 34-45.
Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R.L., Soerjomataram, I., and Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J. Clin. 74(3): 229-263.
Brouns, F. (2002). Soya isoflavones: a new and promising ingredient for the health foods sector. Int. Food Res. 35(2-3): 187-193.
Busby, M.G., Jeffcoat, A.R., Bloedon, L.T., Koch, M.A., Black, T., Dix, K.J., Heizer, W.D., Thomas, B.F., Hill, J.M., and Crowell, J.A. (2002). Clinical characteristics and pharmacokinetics of purified soy isoflavones: single-dose administration to healthy men. Am J Clin Nutr 75(1): 126-136.
Bustamante-Rangel, M., Delgado-Zamarreño, M.M., Pérez-Martín, L., Rodríguez-Gonzalo, E., and Domínguez-Álvarez, J. (2018). Analysis of Isoflavones in Foods. Compr. Rev. Food Sci. Food Saf. 17(2): 391-411. doi: 10.1111/1541-4337.12325.
Carroll, K.K. (1991). Review of clinical studies on cholesterol-lowering response to soy protein. J Am Diet Assoc. 91(7): 820-828.
Chalvon-Demersay, T., Azzout-Marniche, D., Arfsten, J., Egli, L., Gaudichon, C., Karagounis, L.G., and Tomé, D. (2017). A systematic review of the effects of plant compared with animal protein sources on features of metabolic syndrome. J Nutr 147(3): 281-292.
Charalambous, C., Pitta, C.A., and Constantinou, A.I. (2013). Equol enhances tamoxifen’s anti-tumor activity by induction of caspase-mediated apoptosis in MCF-7 breast cancer cells. BMC cancer 13: 1-10.
Chehelgerdi, M., Chehelgerdi, M., Allela, O.Q.B., Pecho, R.D.C., Jayasankar, N., Rao, D.P., Thamaraikani, T., Vasanthan, M., Viktor, P., and Lakshmaiya, N. (2023). Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation. Mol. Cancer 22(1): 169.
Chen, M., Lin, C., and Liu, C. (2015). Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric 18(2): 260-269.
Chen, M., Rao, Y., Zheng, Y., Wei, S., Li, Y., Guo, T., and Yin, P. (2014). Association between soy isoflavone intake and breast cancer risk for pre-and post-menopausal women: a meta-analysis of epidemiological studies. PloS One 9(2): e89288.
Chen, W.-F., Huang, M.-H., Tzang, C.-H., Yang, M., and Wong, M.-S. (2003). Inhibitory actions of genistein in human breast cancer (MCF-7) cells. Biochim Biophys Acta 1638(2): 187-196.
de Vargas, B.A., Bidone, J., Oliveira, L.K., Koester, L.S., Bassani, V.L., and Teixeira, H.F. (2012). Development of topical hydrogels containing genistein-loaded nanoemulsions. J. Biomed. Nanotechnol. 8(2): 330-336.
Del Gaudio, P., Sansone, F., Mencherini, T., De Cicco, F., Russo, P., and Aquino, R.P. (2017). Nanospray drying as a novel tool to improve technological properties of soy isoflavone extracts. Planta Med. 83(05): 426-433.
Deshmukh, K., and Amin, P. (2013). Formulation and evaluation of solid–lipid nanoparticle based 0.1% Soy isoflavone dermal gels. J Pharm BioSci 1: 7-18.
Dong, J.-Y., and Qin, L.-Q. (2011). Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies.    Breast Cancer Res. Treat. 125: 315-323.
Du, Z., Dou, X., Huang, C., Gao, J., Hu, L., Zhu, J., Qian, Y., Dou, M., and Fan, C. (2013). Preparation, drug releasing property and pharmacodynamics of soy isoflavone-loaded chitosan microspheres. Plos One 8(11): e79698.
Dumitrescu, R., and Cotarla, I. (2005). Understanding breast cancer risk‐where do we stand in 2005? J Cell Mol Med 9(1): 208-221.
Emeje, M.O., Obidike, I.C., Akpabio, E.I., and Ofoefule, S.I. (2012). Nanotechnology in drug delivery. Rec. adv. Nov. drug Carri. System 1(4): 69-106.
Gao, R., Lin, P., Yang, W., Fang, Z., Gao, C., Cheng, B., Fang, J., and Yu, W. (2024). Bio-Inspired Nanodelivery Platform: Platelet Membrane-Cloaked Genistein Nanosystem for Targeted Lung Cancer Therapy. Int J Nanomedicine: 10455-10478.
Gao, S., and Hu, M. (2010). Bioavailability challenges associated with development of anti-cancer phenolics. Mini-Rev. Med. Chem. 10(6): 550-567.
Gilbert, E.R., and Liu, D. (2013). Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic β-cell function. Food Funct 4(2): 200-212. doi: 10.1039/c2fo30199g.
Gómez-Zorita, S., González-Arceo, M., Fernández-Quintela, A., Eseberri, I., Trepiana, J., and Portillo, M.P. (2020). Scientific evidence supporting the beneficial effects of isoflavones on human health. J. Nutr. 12(12): 3853.
Hafner, A., Lovrić, J., Lakoš, G.P., and Pepić, I. (2014). Nanotherapeutics in the EU: an overview on current state and future directions. Int J Nanomedicine 9: 1005-1023. doi: 10.2147/ijn.S55359.
Hamburg, M.A. (2012). FDA's approach to regulation of products of nanotechnology. Science 336(6079): 299-300.
Han, H.J., Ekweremadu, C., and Patel, N. (2019). Advanced drug delivery system with nanomaterials for personalised medicine to treat breast cancer. J. Drug Deliv. Technol. 52: 1051-1060.
He, F.-J., and Chen, J.-Q. (2013). Consumption of soybean, soy foods, soy isoflavones and breast cancer incidence: Differences between Chinese women and women in Western countries and possible mechanisms. Food Sci. Hum. Wellness. 2(3-4): 146-161.
Horn-Ross, P.L., John, E.M., Canchola, A.J., Stewart, S.L., and Lee, M.M. (2003). Phytoestrogen intake and endometrial cancer risk. J Natl Cancer Inst 95(15): 1158-1164.
Hossain, M.A., and Rahman, S.M. (2015). Isolation and characterisation of flavonoids from the leaves of medicinal plant Orthosiphon stamineus. Arab. J. Chem. 8(2): 218-221.
Howes, L.G., Howes, J.B., and Knight, D.C. (2006). Isoflavone therapy for menopausal flushes: a systematic review and meta-analysis. Maturitas 55(3): 203-211.
Hsu, E.L., Chen, N., Westbrook, A., Wang, F., Zhang, R., Taylor, R.T., and Hankinson, O. (2009). Modulation of CXCR4, CXCL12, and tumor cell invasion potential in vitro by phytochemicals. J. Oncol. 2009(1): 491985.
Jin, S., Zhang, Q., Kang, X., Wang, J., and Zhao, W. (2010). Daidzein induces MCF-7 breast cancer cell apoptosis via the mitochondrial pathway. Ann. Oncol. 21(2): 263-268.
Kim, I.S., Kim, C.H., and Yang, W.S. (2021). Physiologically Active Molecules and Functional Properties of Soybeans in Human Health-A Current Perspective. Int J Mol Sci 22(8). doi: 10.3390/ijms22084054.
Křížová, L., Dadáková, K., Kašparovská, J., and Kašparovský, T. (2019). Isoflavones. Molecules 24(6): 1076.
Kurzer, M.S., and Xu, X. (1997). Dietary phytoestrogens. Annu. Rev. Nutr. 17(1): 353-381.
Lee, W.-Y., Huang, S.-C., Tzeng, C.-C., Chang, T.-L., and Hsu, K.-F. (2007). Alterations of metastasis-related genes identified using an oligonucleotide microarray of genistein-treated HCC1395 breast cancer cells. HNUC 58(2): 239-246.
Lei, S., Zheng, R., Zhang, S., Wang, S., Chen, R., Sun, K., Zeng, H., Zhou, J., and Wei, W. (2021). Global patterns of breast cancer incidence and mortality: A population‐based cancer registry data analysis from 2000 to 2020. Cancer Commun. 41(11): 1183-1194.
Lethaby, A., Marjoribanks, J., Kronenberg, F., Roberts, H., Eden, J., and Brown, J. (2007). Phytoestrogens for vasomotor menopausal symptoms. Cochrane Database Syst Rev (4).
Li, Y., Miao, W., He, D., Wang, S., Lou, J., Jiang, Y., and Wang, S. (2021). Recent progress on immunotherapy for breast cancer: tumor microenvironment, nanotechnology and more. Front. Bioeng. Biotechnol. 9: 680315.
Li, Z., Li, J., Mo, B., Hu, C., Liu, H., Qi, H., Wang, X., and Xu, J. (2008). Genistein induces cell apoptosis in MDA-MB-231 breast cancer cells via the mitogen-activated protein kinase pathway. In Vitro Toxicol. 22(7): 1749-1753.
Liu, B., Thum, C., Wang, Q., Feng, C., Li, T., Victorelli, F.D., Li, X., Chang, R., Chen, S., and Gong, Y. (2023). The fortification of encapsulated soy isoflavones and texture modification of soy milk by α-lactalbumin nanotubes. Food Chem. 419: 135979.
Liu, Q., Sun, Y., Cheng, J., and Guo, M. (2022). Development of whey protein nanoparticles as carriers to deliver soy isoflavones. LWT-Food Sci Technol 155: 112953.
Lucki, N.C., and Sewer, M.B. (2011). Genistein stimulates MCF-7 breast cancer cell growth by inducing acid ceramidase (ASAH1) gene expression. J. Biol. Chem. 286(22): 19399-19409.
Mejia, S.B., Messina, M., Li, S.S., Viguiliouk, E., Chiavaroli, L., Khan, T.A., Srichaikul, K., Mirrahimi, A., Sievenpiper, J.L., and Kris-Etherton, P. (2019). A meta-analysis of 46 studies identified by the FDA demonstrates that soy protein decreases circulating LDL and total cholesterol concentrations in adults. J Nutr 149(6): 968-981.
Messina, M., and Hilakivi-Clarke, L. (2009). Early intake appears to be the key to the proposed protective effects of soy intake against breast cancer. Nutr Cancer 61(6): 792-798.
Messina, M., Kucuk, O., and Lampe, J.W. (2006a). An overview of the health effects of isoflavones with an emphasis on prostate cancer risk and prostate-specific antigen levels. J. AOAC Int. 89(4): 1121-1134.
Messina, M., Nagata, C., and Wu, A.H. (2006b). Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer 55(1): 1-12.
Mezei, O., Banz, W.J., Steger, R.W., Peluso, M.R., Winters, T.A., and Shay, N. (2003). Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells. J Nutr 133(5): 1238-1243. doi: 10.1093/jn/133.5.1238.
Mo, H., Chen, X., Cui, B., Chen, Y., Chen, M., Xu, Z., Wen, L., Cheng, Y., and Jiao, Y. (2023). Formation and Characterization of Self-Assembled Rice Protein Hydrolysate Nanoparticles as Soy Isoflavone Delivery Systems. Foods 12(7): 1523.
More, M.P., Pardeshi, S.R., Pardeshi, C.V., Sonawane, G.A., Shinde, M.N., Deshmukh, P.K., Naik, J.B., and Kulkarni, A.D. (2021). Recent advances in phytochemical-based Nano-formulation for drug-resistant Cancer. Med. Drug Discov. 10: 100082.
Morito, K., Hirose, T., Kinjo, J., Hirakawa, T., Okawa, M., Nohara, T., Ogawa, S., Inoue, S., Muramatsu, M., and Masamune, Y. (2001). Interaction of phytoestrogens with estrogen receptors α and β. Biol Pharm Bull 24(4): 351-356.
Nasrollahzadeh, M., Sajadi, S.M., Sajjadi, M., and Issaabadi, Z. (2019). "An introduction to nanotechnology," in Int. Sci. Technol.: Elsevier), 1-27.
Nemitz, M.C., von Poser, G.L., and Teixeira, H.F. (2019). In vitro skin permeation/retention of daidzein, genistein and glycitein from a soybean isoflavone rich fraction-loaded nanoemulsions and derived hydrogels. J. Drug Deliv. Technol. 51: 63-69.
Obiorah, I.E., Fan, P., and Jordan, V.C. (2014). Breast cancer cell apoptosis with phytoestrogens is dependent on an estrogen-deprived state. Cancer Prev. Res. 7(9): 939-949.
Onoe, Y., Miyaura, C., Ohta, H., Nozawa, S., and Suda, T. (1997). Expression of estrogen receptor β in rat bone. Endocrinol. 138(10): 4509-4512.
Pan, H., Zhou, W., He, W., Liu, X., Ding, Q., Ling, L., Zha, X., and Wang, S. (2012). Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway. Int. J. Mol. Med. 30(2): 337-343.
Phan, V., Walters, J., Brownlow, B., and Elbayoumi, T. (2013). Enhanced cytotoxicity of optimized liposomal genistein via specific induction of apoptosis in breast, ovarian and prostate carcinomas. J. Drug Target. 21(10): 1001-1011.
Pietta, P.-G. (2000). Flavonoids as antioxidants. J. Nat. Prod. 63(7): 1035-1042.
Pool, H., Campos-Vega, R., Herrera-Hernández, M.G., García-Solis, P., García-Gasca, T., Sánchez, I.C., Luna-Bárcenas, G., and Vergara-Castañeda, H. (2018). Development of genistein-PEGylated silica hybrid nanomaterials with enhanced antioxidant and antiproliferative properties on HT29 human colon cancer cells. Am. J. Transl. Res. 10(8): 2306.
Qin, L.-Q., Xu, J.-Y., Wang, P.-Y., and Hoshi, K. (2006). Soyfood intake in the prevention of breast cancer risk in women: a meta-analysis of observational epidemiological studies. J Nutr Sci Vitaminol 52(6): 428-436.
Rizzo, G., and Baroni, L. (2018). Soy, soy foods and their role in vegetarian diets. J. Nutr. 10(1): 43.
Sainz, V., Conniot, J., Matos, A.I., Peres, C., Zupanǒiǒ, E., Moura, L., Silva, L.C., Florindo, H.F., and Gaspar, R.S. (2015). Regulatory aspects on nanomedicines. Biochem. Biophys. Res. Commun. 468(3): 504-510.
Sakamoto, T., Horiguchi, H., Oguma, E., and Kayama, F. (2010). Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells. J. Nutr. Biochem. 21(9): 856-864.
Sarkar, N., and Bose, S. (2020). Controlled release of soy isoflavones from multifunctional 3D printed bone tissue engineering scaffolds. Acta Biomater. 114: 407-420.
Setchell, K.D., Brzezinski, A., Brown, N.M., Desai, P.B., Melhem, M., Meredith, T., Zimmer-Nechimias, L., Wolfe, B., Cohen, Y., and Blatt, Y. (2005). Pharmacokinetics of a slow-release formulation of soybean isoflavones in healthy postmenopausal women. J. Agric. Food Chem. 53(6): 1938-1944.
Setchell, K.D., and Cassidy, A. (1999). Dietary isoflavones: biological effects and relevance to human health. J. Nutr. 129(3): 758S-767S.
Silva, A., Nunes, B., De Oliveira, M., Koester, L.S., Mayorga, P., Bassani, V.L., and Teixeira, H.F. (2009). Development of topical nanoemulsions containing the isoflavone genistein. Die Pharmazie-Int. J. Pharm. Sci. 64(1): 32-35.
Silva, H. (2021). The vascular effects of isolated isoflavones—A focus on the determinants of blood pressure regulation. Biology 10(1): 49.
Sindhu, R.K., Verma, R., Salgotra, T., Rahman, M.H., Shah, M., Akter, R., Murad, W., Mubin, S., Bibi, P., and Qusti, S. (2021). Impacting the remedial potential of nano delivery-based flavonoids for breast cancer treatment. Molecules 26(17): 5163.
Sohn, S.I., Pandian, S., Oh, Y.J., Kang, H.J., Cho, W.S., and Cho, Y.S. (2021). Metabolic engineering of isoflavones: an updated overview. Front. Plant Sci. 12: 670103.
Spagnuolo, C., Russo, G.L., Orhan, I.E., Habtemariam, S., Daglia, M., Sureda, A., Nabavi, S.F., Devi, K.P., Loizzo, M.R., and Tundis, R. (2015). Genistein and cancer: current status, challenges, and future directions. Adv Nutr 6(4): 408-419.
Spoerlein, C., Mahal, K., Schmidt, H., and Schobert, R. (2013). Effects of chrysin, apigenin, genistein and their homoleptic copper (II) complexes on the growth and metastatic potential of cancer cells. J. Inorg. Biochem. 127: 107-115.
Su, S.-J., Chow, N.-H., Kung, M.-L., Hung, T.-C., and Chang, K.-L. (2003). Effects of soy isoflavones on apoptosis induction and G2-M arrest in human hepatoma cells involvement of caspase-3 activation, Bcl-2 and Bcl-XL downregulation, and Cdc2 kinase activity. Nutr. Cancer 45(1): 113-123.
Sun, Y., Liu, Z., and Wang, J. (2011). Ultrasound-assisted extraction of five isoflavones from Iris tectorum Maxim. Sep. Purif. Technol. 78(1): 49-54.
Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., and Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3): 209-249.
Suzuki, T., Matsuo, K., Tsunoda, N., Hirose, K., Hiraki, A., Kawase, T., Yamashita, T., Iwata, H., Tanaka, H., and Tajima, K. (2008). Effect of soybean on breast cancer according to receptor status: a case–control study in Japan. Int. J. Cancer 123(7): 1674-1680.
Taku, K., Melby, M.K., Takebayashi, J., Mizuno, S., Ishimi, Y., Omori, T., and Watanabe, S. (2010). Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials. Asia Pacific journal of clinical nutrition 19(1): 33-42.
Tham, D.M., Gardner, C.D., and Haskell, W.L. (1998). Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab. 83(7): 2223-2235.
Tian, M., Cheng, J., and Guo, M. (2024). Stability, Digestion, and Cellular Transport of Soy Isoflavones Nanoparticles Stabilized by Polymerized Goat Milk Whey Protein. Antioxidants 13(5): 567.
Tian, M., Wang, C., Cheng, J., Wang, H., Jiang, S., and Guo, M. (2020). Preparation and characterization of soy isoflavones nanoparticles using polymerized goat milk whey protein as wall material. Foods 9(9): 1198.
Tran, P., Lee, S.-E., Kim, D.-H., Pyo, Y.-C., and Park, J.-S. (2020). Recent advances of nanotechnology for the delivery of anticancer drugs for breast cancer treatment. J. Pharm. Investig. 50: 261-270.
Umeno, A., Horie, M., Murotomi, K., Nakajima, Y., and Yoshida, Y. (2016). Antioxidative and antidiabetic effects of natural polyphenols and isoflavones. Molecules 21(6): 708.
Van der Eecken, H., Joniau, S., Berghen, C., Rans, K., and De Meerleer, G. (2023). The use of soy isoflavones in the treatment of prostate cancer: a focus on the cellular effects. Nutrients 15(23): 4856.
Wang, H.-J., and Murphy, P.A. (1994a). Isoflavone composition of American and Japanese soybeans in Iowa: effects of variety, crop year, and location. J. Agric. Food Chem. 42(8): 1674-1677.
Wang, H.-j., and Murphy, P.A. (1994b). Isoflavone content in commercial soybean foods. J. Agric. Food Chem. 42(8): 1666-1673.
Wang, P.-P., Luo, Z.-G., and Peng, X.-C. (2018). Encapsulation of vitamin E and soy isoflavone using spiral dextrin: Comparative structural characterization, release kinetics, and antioxidant capacity during simulated gastrointestinal tract. J. Agric. Food Chem. 66(40): 10598-10607.
Wang, S., Shao, G., Yang, J., Liu, J., Wang, J., Zhao, H., Yang, L., Liu, H., Zhu, D., and Li, Y. (2020). The production of gel beads of soybean hull polysaccharides loaded with soy isoflavone and their pH-dependent release. Food Chem. 313: 126095.
Wei, H., Bowen, R., Cai, Q., Barnes, S., and Wang, Y. (1995). Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exp Biol Med 208(1): 124-130. doi: 10.3181/00379727-208-43844.
Wei, Y., Lv, J., Guo, Y., Bian, Z., Gao, M., Du, H., Yang, L., Chen, Y., Zhang, X., and Wang, T. (2020). Soy intake and breast cancer risk: A prospective study of 300,000 Chinese women and a dose–response meta-analysis. Eur. J. Epidemiol. 35: 567-578.
Wójciak, M., Drozdowski, P., Skalska-Kamińska, A., Zagórska-Dziok, M., Ziemlewska, A., Nizioł-Łukaszewska, Z., and Latalska, M. (2024). Protective, anti-inflammatory, and anti-aging effects of soy isoflavones on skin cells: An overview of in vitro and in vivo studies. Molecules 29(23). doi: 10.3390/molecules29235790.
Wu, A.H., Yu, M.C., Tseng, C.-C., and Pike, M.C. (2008). Epidemiology of soy exposures and breast cancer risk. Br. J. Cancer 98(1): 9-14.
Xiao, C.W. (2008). Health effects of soy protein and isoflavones in humans. J Nutr. 138(6): 1244S-1249S.
Yang, S., Zhou, Q., and Yang, X. (2007). Caspase-3 status is a determinant of the differential responses to genistein between MDA-MB-231 and MCF-7 breast cancer cells. Biochim. Biophys. Acta, Mol. Cell Res. 1773(6): 903-911.
Ye, Y.-B., Tang, X.-Y., Verbruggen, M.A., and Su, Y.-X. (2006). Soy isoflavones attenuate bone loss in early postmenopausal Chinese women: a single-blind randomized, placebo-controlled trial. Eur. J. Nutr. 45: 327-334.
Zaheer, K., and Humayoun Akhtar, M. (2017). An updated review of dietary isoflavones: Nutrition, processing, bioavailability and impacts on human health. Crit Rev Food Sci Nutr 57(6): 1280-1293.
Zhang, X., Veliky, C.V., Birru, R.L., Barinas-Mitchell, E., Magnani, J.W., and Sekikawa, A. (2021). Potential protective effects of equol (soy isoflavone metabolite) on coronary heart diseases—from molecular mechanisms to studies in humans. Nutrients 13(11): 3739.
 
 
 
 
 
 
Ahmad, A., Biersack, B., Li, Y., Kong, D., Bao, B., Schobert, R., B. Padhye, S., and H. Sarkar, F. (2013). Deregulation of PI3K/Akt/mTOR signaling pathways by isoflavones and its implication in cancer treatment. Anti-Cancer Agents Med. Chem. 13(7): 1014-1024.
Amawi, H., Ashby, C.R., and Tiwari, A.K. (2017). Cancer chemoprevention through dietary flavonoids: what’s limiting? Chin. J. Cancer 36: 1-13.
Andreani, T., Cheng, R., Elbadri, K., Ferro, C., Menezes, T., Dos Santos, M.R., Pereira, C.M., and Santos, H.A. (2024). Natural compounds-based nanomedicines for cancer treatment: Future directions and challenges. Drug Deliv Transl Res 14(10): 2845-2916.
Baglia, M.L., Zheng, W., Li, H., Yang, G., Gao, J., Gao, Y.T., and Shu, X.O. (2016). The association of soy food consumption with the risk of subtype of breast cancers defined by hormone receptor and HER2 status. Int J Cancer 139(4): 742-748.
Barańska, A., Kanadys, W., Bogdan, M., Stępień, E., Barczyński, B., Kłak, A., Augustynowicz, A., Szajnik, M., and Religioni, U. (2022). The role of soy isoflavones in the prevention of bone loss in postmenopausal women: A systematic review with meta-analysis of randomized controlled trials. J. Clin. Med. 11(16): 4676.
Barnard, N.D., Kahleova, H., Holtz, D.N., Del Aguila, F., Neola, M., Crosby, L.M., and Holubkov, R. (2021). The Women's Study for the Alleviation of Vasomotor Symptoms (WAVS): a randomized, controlled trial of a plant-based diet and whole soybeans for postmenopausal women. Menopause 28(10): 1150-1156. doi: 10.1097/gme.0000000000001812.
Blicharski, T., and Oniszczuk, A. (2017). Extraction methods for the isolation of isoflavonoids from plant material. Open Chem. 15(1): 34-45.
Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R.L., Soerjomataram, I., and Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J. Clin. 74(3): 229-263.
Brouns, F. (2002). Soya isoflavones: a new and promising ingredient for the health foods sector. Int. Food Res. 35(2-3): 187-193.
Busby, M.G., Jeffcoat, A.R., Bloedon, L.T., Koch, M.A., Black, T., Dix, K.J., Heizer, W.D., Thomas, B.F., Hill, J.M., and Crowell, J.A. (2002). Clinical characteristics and pharmacokinetics of purified soy isoflavones: single-dose administration to healthy men. Am J Clin Nutr 75(1): 126-136.
Bustamante-Rangel, M., Delgado-Zamarreño, M.M., Pérez-Martín, L., Rodríguez-Gonzalo, E., and Domínguez-Álvarez, J. (2018). Analysis of Isoflavones in Foods. Compr. Rev. Food Sci. Food Saf. 17(2): 391-411. doi: 10.1111/1541-4337.12325.
Carroll, K.K. (1991). Review of clinical studies on cholesterol-lowering response to soy protein. J Am Diet Assoc. 91(7): 820-828.
Chalvon-Demersay, T., Azzout-Marniche, D., Arfsten, J., Egli, L., Gaudichon, C., Karagounis, L.G., and Tomé, D. (2017). A systematic review of the effects of plant compared with animal protein sources on features of metabolic syndrome. J Nutr 147(3): 281-292.
Charalambous, C., Pitta, C.A., and Constantinou, A.I. (2013). Equol enhances tamoxifen’s anti-tumor activity by induction of caspase-mediated apoptosis in MCF-7 breast cancer cells. BMC cancer 13: 1-10.
Chehelgerdi, M., Chehelgerdi, M., Allela, O.Q.B., Pecho, R.D.C., Jayasankar, N., Rao, D.P., Thamaraikani, T., Vasanthan, M., Viktor, P., and Lakshmaiya, N. (2023). Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation. Mol. Cancer 22(1): 169.
Chen, M., Lin, C., and Liu, C. (2015). Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric 18(2): 260-269.
Chen, M., Rao, Y., Zheng, Y., Wei, S., Li, Y., Guo, T., and Yin, P. (2014). Association between soy isoflavone intake and breast cancer risk for pre-and post-menopausal women: a meta-analysis of epidemiological studies. PloS One 9(2): e89288.
Chen, W.-F., Huang, M.-H., Tzang, C.-H., Yang, M., and Wong, M.-S. (2003). Inhibitory actions of genistein in human breast cancer (MCF-7) cells. Biochim Biophys Acta 1638(2): 187-196.
de Vargas, B.A., Bidone, J., Oliveira, L.K., Koester, L.S., Bassani, V.L., and Teixeira, H.F. (2012). Development of topical hydrogels containing genistein-loaded nanoemulsions. J. Biomed. Nanotechnol. 8(2): 330-336.
Del Gaudio, P., Sansone, F., Mencherini, T., De Cicco, F., Russo, P., and Aquino, R.P. (2017). Nanospray drying as a novel tool to improve technological properties of soy isoflavone extracts. Planta Med. 83(05): 426-433.
Deshmukh, K., and Amin, P. (2013). Formulation and evaluation of solid–lipid nanoparticle based 0.1% Soy isoflavone dermal gels. J Pharm BioSci 1: 7-18.
Dong, J.-Y., and Qin, L.-Q. (2011). Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies.    Breast Cancer Res. Treat. 125: 315-323.
Du, Z., Dou, X., Huang, C., Gao, J., Hu, L., Zhu, J., Qian, Y., Dou, M., and Fan, C. (2013). Preparation, drug releasing property and pharmacodynamics of soy isoflavone-loaded chitosan microspheres. Plos One 8(11): e79698.
Dumitrescu, R., and Cotarla, I. (2005). Understanding breast cancer risk‐where do we stand in 2005? J Cell Mol Med 9(1): 208-221.
Emeje, M.O., Obidike, I.C., Akpabio, E.I., and Ofoefule, S.I. (2012). Nanotechnology in drug delivery. Rec. adv. Nov. drug Carri. System 1(4): 69-106.
Gao, R., Lin, P., Yang, W., Fang, Z., Gao, C., Cheng, B., Fang, J., and Yu, W. (2024). Bio-Inspired Nanodelivery Platform: Platelet Membrane-Cloaked Genistein Nanosystem for Targeted Lung Cancer Therapy. Int J Nanomedicine: 10455-10478.
Gao, S., and Hu, M. (2010). Bioavailability challenges associated with development of anti-cancer phenolics. Mini-Rev. Med. Chem. 10(6): 550-567.
Gilbert, E.R., and Liu, D. (2013). Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic β-cell function. Food Funct 4(2): 200-212. doi: 10.1039/c2fo30199g.
Gómez-Zorita, S., González-Arceo, M., Fernández-Quintela, A., Eseberri, I., Trepiana, J., and Portillo, M.P. (2020). Scientific evidence supporting the beneficial effects of isoflavones on human health. J. Nutr. 12(12): 3853.
Hafner, A., Lovrić, J., Lakoš, G.P., and Pepić, I. (2014). Nanotherapeutics in the EU: an overview on current state and future directions. Int J Nanomedicine 9: 1005-1023. doi: 10.2147/ijn.S55359.
Hamburg, M.A. (2012). FDA's approach to regulation of products of nanotechnology. Science 336(6079): 299-300.
Han, H.J., Ekweremadu, C., and Patel, N. (2019). Advanced drug delivery system with nanomaterials for personalised medicine to treat breast cancer. J. Drug Deliv. Technol. 52: 1051-1060.
He, F.-J., and Chen, J.-Q. (2013). Consumption of soybean, soy foods, soy isoflavones and breast cancer incidence: Differences between Chinese women and women in Western countries and possible mechanisms. Food Sci. Hum. Wellness. 2(3-4): 146-161.
Horn-Ross, P.L., John, E.M., Canchola, A.J., Stewart, S.L., and Lee, M.M. (2003). Phytoestrogen intake and endometrial cancer risk. J Natl Cancer Inst 95(15): 1158-1164.
Hossain, M.A., and Rahman, S.M. (2015). Isolation and characterisation of flavonoids from the leaves of medicinal plant Orthosiphon stamineus. Arab. J. Chem. 8(2): 218-221.
Howes, L.G., Howes, J.B., and Knight, D.C. (2006). Isoflavone therapy for menopausal flushes: a systematic review and meta-analysis. Maturitas 55(3): 203-211.
Hsu, E.L., Chen, N., Westbrook, A., Wang, F., Zhang, R., Taylor, R.T., and Hankinson, O. (2009). Modulation of CXCR4, CXCL12, and tumor cell invasion potential in vitro by phytochemicals. J. Oncol. 2009(1): 491985.
Jin, S., Zhang, Q., Kang, X., Wang, J., and Zhao, W. (2010). Daidzein induces MCF-7 breast cancer cell apoptosis via the mitochondrial pathway. Ann. Oncol. 21(2): 263-268.
Kim, I.S., Kim, C.H., and Yang, W.S. (2021). Physiologically Active Molecules and Functional Properties of Soybeans in Human Health-A Current Perspective. Int J Mol Sci 22(8). doi: 10.3390/ijms22084054.
Křížová, L., Dadáková, K., Kašparovská, J., and Kašparovský, T. (2019). Isoflavones. Molecules 24(6): 1076.
Kurzer, M.S., and Xu, X. (1997). Dietary phytoestrogens. Annu. Rev. Nutr. 17(1): 353-381.
Lee, W.-Y., Huang, S.-C., Tzeng, C.-C., Chang, T.-L., and Hsu, K.-F. (2007). Alterations of metastasis-related genes identified using an oligonucleotide microarray of genistein-treated HCC1395 breast cancer cells. HNUC 58(2): 239-246.
Lei, S., Zheng, R., Zhang, S., Wang, S., Chen, R., Sun, K., Zeng, H., Zhou, J., and Wei, W. (2021). Global patterns of breast cancer incidence and mortality: A population‐based cancer registry data analysis from 2000 to 2020. Cancer Commun. 41(11): 1183-1194.
Lethaby, A., Marjoribanks, J., Kronenberg, F., Roberts, H., Eden, J., and Brown, J. (2007). Phytoestrogens for vasomotor menopausal symptoms. Cochrane Database Syst Rev (4).
Li, Y., Miao, W., He, D., Wang, S., Lou, J., Jiang, Y., and Wang, S. (2021). Recent progress on immunotherapy for breast cancer: tumor microenvironment, nanotechnology and more. Front. Bioeng. Biotechnol. 9: 680315.
Li, Z., Li, J., Mo, B., Hu, C., Liu, H., Qi, H., Wang, X., and Xu, J. (2008). Genistein induces cell apoptosis in MDA-MB-231 breast cancer cells via the mitogen-activated protein kinase pathway. In Vitro Toxicol. 22(7): 1749-1753.
Liu, B., Thum, C., Wang, Q., Feng, C., Li, T., Victorelli, F.D., Li, X., Chang, R., Chen, S., and Gong, Y. (2023). The fortification of encapsulated soy isoflavones and texture modification of soy milk by α-lactalbumin nanotubes. Food Chem. 419: 135979.
Liu, Q., Sun, Y., Cheng, J., and Guo, M. (2022). Development of whey protein nanoparticles as carriers to deliver soy isoflavones. LWT-Food Sci Technol 155: 112953.
Lucki, N.C., and Sewer, M.B. (2011). Genistein stimulates MCF-7 breast cancer cell growth by inducing acid ceramidase (ASAH1) gene expression. J. Biol. Chem. 286(22): 19399-19409.
Mejia, S.B., Messina, M., Li, S.S., Viguiliouk, E., Chiavaroli, L., Khan, T.A., Srichaikul, K., Mirrahimi, A., Sievenpiper, J.L., and Kris-Etherton, P. (2019). A meta-analysis of 46 studies identified by the FDA demonstrates that soy protein decreases circulating LDL and total cholesterol concentrations in adults. J Nutr 149(6): 968-981.
Messina, M., and Hilakivi-Clarke, L. (2009). Early intake appears to be the key to the proposed protective effects of soy intake against breast cancer. Nutr Cancer 61(6): 792-798.
Messina, M., Kucuk, O., and Lampe, J.W. (2006a). An overview of the health effects of isoflavones with an emphasis on prostate cancer risk and prostate-specific antigen levels. J. AOAC Int. 89(4): 1121-1134.
Messina, M., Nagata, C., and Wu, A.H. (2006b). Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer 55(1): 1-12.
Mezei, O., Banz, W.J., Steger, R.W., Peluso, M.R., Winters, T.A., and Shay, N. (2003). Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells. J Nutr 133(5): 1238-1243. doi: 10.1093/jn/133.5.1238.
Mo, H., Chen, X., Cui, B., Chen, Y., Chen, M., Xu, Z., Wen, L., Cheng, Y., and Jiao, Y. (2023). Formation and Characterization of Self-Assembled Rice Protein Hydrolysate Nanoparticles as Soy Isoflavone Delivery Systems. Foods 12(7): 1523.
More, M.P., Pardeshi, S.R., Pardeshi, C.V., Sonawane, G.A., Shinde, M.N., Deshmukh, P.K., Naik, J.B., and Kulkarni, A.D. (2021). Recent advances in phytochemical-based Nano-formulation for drug-resistant Cancer. Med. Drug Discov. 10: 100082.
Morito, K., Hirose, T., Kinjo, J., Hirakawa, T., Okawa, M., Nohara, T., Ogawa, S., Inoue, S., Muramatsu, M., and Masamune, Y. (2001). Interaction of phytoestrogens with estrogen receptors α and β. Biol Pharm Bull 24(4): 351-356.
Nasrollahzadeh, M., Sajadi, S.M., Sajjadi, M., and Issaabadi, Z. (2019). "An introduction to nanotechnology," in Int. Sci. Technol.: Elsevier), 1-27.
Nemitz, M.C., von Poser, G.L., and Teixeira, H.F. (2019). In vitro skin permeation/retention of daidzein, genistein and glycitein from a soybean isoflavone rich fraction-loaded nanoemulsions and derived hydrogels. J. Drug Deliv. Technol. 51: 63-69.
Obiorah, I.E., Fan, P., and Jordan, V.C. (2014). Breast cancer cell apoptosis with phytoestrogens is dependent on an estrogen-deprived state. Cancer Prev. Res. 7(9): 939-949.
Onoe, Y., Miyaura, C., Ohta, H., Nozawa, S., and Suda, T. (1997). Expression of estrogen receptor β in rat bone. Endocrinol. 138(10): 4509-4512.
Pan, H., Zhou, W., He, W., Liu, X., Ding, Q., Ling, L., Zha, X., and Wang, S. (2012). Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway. Int. J. Mol. Med. 30(2): 337-343.
Phan, V., Walters, J., Brownlow, B., and Elbayoumi, T. (2013). Enhanced cytotoxicity of optimized liposomal genistein via specific induction of apoptosis in breast, ovarian and prostate carcinomas. J. Drug Target. 21(10): 1001-1011.
Pietta, P.-G. (2000). Flavonoids as antioxidants. J. Nat. Prod. 63(7): 1035-1042.
Pool, H., Campos-Vega, R., Herrera-Hernández, M.G., García-Solis, P., García-Gasca, T., Sánchez, I.C., Luna-Bárcenas, G., and Vergara-Castañeda, H. (2018). Development of genistein-PEGylated silica hybrid nanomaterials with enhanced antioxidant and antiproliferative properties on HT29 human colon cancer cells. Am. J. Transl. Res. 10(8): 2306.
Qin, L.-Q., Xu, J.-Y., Wang, P.-Y., and Hoshi, K. (2006). Soyfood intake in the prevention of breast cancer risk in women: a meta-analysis of observational epidemiological studies. J Nutr Sci Vitaminol 52(6): 428-436.
Rizzo, G., and Baroni, L. (2018). Soy, soy foods and their role in vegetarian diets. J. Nutr. 10(1): 43.
Sainz, V., Conniot, J., Matos, A.I., Peres, C., Zupanǒiǒ, E., Moura, L., Silva, L.C., Florindo, H.F., and Gaspar, R.S. (2015). Regulatory aspects on nanomedicines. Biochem. Biophys. Res. Commun. 468(3): 504-510.
Sakamoto, T., Horiguchi, H., Oguma, E., and Kayama, F. (2010). Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells. J. Nutr. Biochem. 21(9): 856-864.
Sarkar, N., and Bose, S. (2020). Controlled release of soy isoflavones from multifunctional 3D printed bone tissue engineering scaffolds. Acta Biomater. 114: 407-420.
Setchell, K.D., Brzezinski, A., Brown, N.M., Desai, P.B., Melhem, M., Meredith, T., Zimmer-Nechimias, L., Wolfe, B., Cohen, Y., and Blatt, Y. (2005). Pharmacokinetics of a slow-release formulation of soybean isoflavones in healthy postmenopausal women. J. Agric. Food Chem. 53(6): 1938-1944.
Setchell, K.D., and Cassidy, A. (1999). Dietary isoflavones: biological effects and relevance to human health. J. Nutr. 129(3): 758S-767S.
Silva, A., Nunes, B., De Oliveira, M., Koester, L.S., Mayorga, P., Bassani, V.L., and Teixeira, H.F. (2009). Development of topical nanoemulsions containing the isoflavone genistein. Die Pharmazie-Int. J. Pharm. Sci. 64(1): 32-35.
Silva, H. (2021). The vascular effects of isolated isoflavones—A focus on the determinants of blood pressure regulation. Biology 10(1): 49.
Sindhu, R.K., Verma, R., Salgotra, T., Rahman, M.H., Shah, M., Akter, R., Murad, W., Mubin, S., Bibi, P., and Qusti, S. (2021). Impacting the remedial potential of nano delivery-based flavonoids for breast cancer treatment. Molecules 26(17): 5163.
Sohn, S.I., Pandian, S., Oh, Y.J., Kang, H.J., Cho, W.S., and Cho, Y.S. (2021). Metabolic engineering of isoflavones: an updated overview. Front. Plant Sci. 12: 670103.
Spagnuolo, C., Russo, G.L., Orhan, I.E., Habtemariam, S., Daglia, M., Sureda, A., Nabavi, S.F., Devi, K.P., Loizzo, M.R., and Tundis, R. (2015). Genistein and cancer: current status, challenges, and future directions. Adv Nutr 6(4): 408-419.
Spoerlein, C., Mahal, K., Schmidt, H., and Schobert, R. (2013). Effects of chrysin, apigenin, genistein and their homoleptic copper (II) complexes on the growth and metastatic potential of cancer cells. J. Inorg. Biochem. 127: 107-115.
Su, S.-J., Chow, N.-H., Kung, M.-L., Hung, T.-C., and Chang, K.-L. (2003). Effects of soy isoflavones on apoptosis induction and G2-M arrest in human hepatoma cells involvement of caspase-3 activation, Bcl-2 and Bcl-XL downregulation, and Cdc2 kinase activity. Nutr. Cancer 45(1): 113-123.
Sun, Y., Liu, Z., and Wang, J. (2011). Ultrasound-assisted extraction of five isoflavones from Iris tectorum Maxim. Sep. Purif. Technol. 78(1): 49-54.
Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., and Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3): 209-249.
Suzuki, T., Matsuo, K., Tsunoda, N., Hirose, K., Hiraki, A., Kawase, T., Yamashita, T., Iwata, H., Tanaka, H., and Tajima, K. (2008). Effect of soybean on breast cancer according to receptor status: a case–control study in Japan. Int. J. Cancer 123(7): 1674-1680.
Taku, K., Melby, M.K., Takebayashi, J., Mizuno, S., Ishimi, Y., Omori, T., and Watanabe, S. (2010). Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials. Asia Pacific journal of clinical nutrition 19(1): 33-42.
Tham, D.M., Gardner, C.D., and Haskell, W.L. (1998). Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab. 83(7): 2223-2235.
Tian, M., Cheng, J., and Guo, M. (2024). Stability, Digestion, and Cellular Transport of Soy Isoflavones Nanoparticles Stabilized by Polymerized Goat Milk Whey Protein. Antioxidants 13(5): 567.
Tian, M., Wang, C., Cheng, J., Wang, H., Jiang, S., and Guo, M. (2020). Preparation and characterization of soy isoflavones nanoparticles using polymerized goat milk whey protein as wall material. Foods 9(9): 1198.
Tran, P., Lee, S.-E., Kim, D.-H., Pyo, Y.-C., and Park, J.-S. (2020). Recent advances of nanotechnology for the delivery of anticancer drugs for breast cancer treatment. J. Pharm. Investig. 50: 261-270.
Umeno, A., Horie, M., Murotomi, K., Nakajima, Y., and Yoshida, Y. (2016). Antioxidative and antidiabetic effects of natural polyphenols and isoflavones. Molecules 21(6): 708.
Van der Eecken, H., Joniau, S., Berghen, C., Rans, K., and De Meerleer, G. (2023). The use of soy isoflavones in the treatment of prostate cancer: a focus on the cellular effects. Nutrients 15(23): 4856.
Wang, H.-J., and Murphy, P.A. (1994a). Isoflavone composition of American and Japanese soybeans in Iowa: effects of variety, crop year, and location. J. Agric. Food Chem. 42(8): 1674-1677.
Wang, H.-j., and Murphy, P.A. (1994b). Isoflavone content in commercial soybean foods. J. Agric. Food Chem. 42(8): 1666-1673.
Wang, P.-P., Luo, Z.-G., and Peng, X.-C. (2018). Encapsulation of vitamin E and soy isoflavone using spiral dextrin: Comparative structural characterization, release kinetics, and antioxidant capacity during simulated gastrointestinal tract. J. Agric. Food Chem. 66(40): 10598-10607.
Wang, S., Shao, G., Yang, J., Liu, J., Wang, J., Zhao, H., Yang, L., Liu, H., Zhu, D., and Li, Y. (2020). The production of gel beads of soybean hull polysaccharides loaded with soy isoflavone and their pH-dependent release. Food Chem. 313: 126095.
Wei, H., Bowen, R., Cai, Q., Barnes, S., and Wang, Y. (1995). Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exp Biol Med 208(1): 124-130. doi: 10.3181/00379727-208-43844.
Wei, Y., Lv, J., Guo, Y., Bian, Z., Gao, M., Du, H., Yang, L., Chen, Y., Zhang, X., and Wang, T. (2020). Soy intake and breast cancer risk: A prospective study of 300,000 Chinese women and a dose–response meta-analysis. Eur. J. Epidemiol. 35: 567-578.
Wójciak, M., Drozdowski, P., Skalska-Kamińska, A., Zagórska-Dziok, M., Ziemlewska, A., Nizioł-Łukaszewska, Z., and Latalska, M. (2024). Protective, anti-inflammatory, and anti-aging effects of soy isoflavones on skin cells: An overview of in vitro and in vivo studies. Molecules 29(23). doi: 10.3390/molecules29235790.
Wu, A.H., Yu, M.C., Tseng, C.-C., and Pike, M.C. (2008). Epidemiology of soy exposures and breast cancer risk. Br. J. Cancer 98(1): 9-14.
Xiao, C.W. (2008). Health effects of soy protein and isoflavones in humans. J Nutr. 138(6): 1244S-1249S.
Yang, S., Zhou, Q., and Yang, X. (2007). Caspase-3 status is a determinant of the differential responses to genistein between MDA-MB-231 and MCF-7 breast cancer cells. Biochim. Biophys. Acta, Mol. Cell Res. 1773(6): 903-911.
Ye, Y.-B., Tang, X.-Y., Verbruggen, M.A., and Su, Y.-X. (2006). Soy isoflavones attenuate bone loss in early postmenopausal Chinese women: a single-blind randomized, placebo-controlled trial. Eur. J. Nutr. 45: 327-334.
Zaheer, K., and Humayoun Akhtar, M. (2017). An updated review of dietary isoflavones: Nutrition, processing, bioavailability and impacts on human health. Crit Rev Food Sci Nutr 57(6): 1280-1293.
Zhang, X., Veliky, C.V., Birru, R.L., Barinas-Mitchell, E., Magnani, J.W., and Sekikawa, A. (2021). Potential protective effects of equol (soy isoflavone metabolite) on coronary heart diseases—from molecular mechanisms to studies in humans. Nutrients 13(11): 3739.
 
Journal of Plant Molecular Breeding
Volume 12, Issue 2
December 2024
Pages 133-151

  • Receive Date 05 January 2025
  • Revise Date 15 March 2025
  • Accept Date 17 March 2025
  • First Publish Date 17 March 2025