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Health Benefits and Pharmacological Molecular Properties of Isoflavandiol (Equol): In-silico and in-vitro Updates

  • Pushpendra Singh
  • Prem P. Kushwaha
  • Shashank Kumar
Chapter

Abstract

Equol (EQ) is metabolized product of daidzein which is beneficial for health, related with positive outcome in various diseases such as osteoporosis, cancers, menopausal symptoms, glucose metabolism/diabetes and cardiovascular risk. EQ (isoflavone) has many types of biological functions, including antioxidant, anti-inflammatory, and anticarcinogenic activity. Moreover, it reduces the proliferation, invasion, migration, and survival of the cell in different cancer including breast, hepatocellular, ovarian, and prostate cancer. So isoflavone induced arrest in growth and apoptosis in prostate cancer cell occurs via different mechanisms such as antioxidant defense, and repression of angiogenesis. Further, we studied and concluded in silico and in vitro anticancer activity of EQ. We performed multitargeted molecular docking of EQ with 20 over expressed proteins (Proteins involved in different diseases) employing molecular docking approach. Docking result shows that VEGFR2, PI3K, AR, and ER have good Gscore against EQ. Moreover, it has seen that many weak interactions like hydrogen bonding, hydrophobic and van der Walls interactions are the key player in protein-EQ interactions. Docking result of EQ with different proteins, summarize the various bonding energy, hydrogen bond, and electrostatic bond. Furthermore, chart out various ADME/T properties of EQ which are conclusive for drug-like properties.

Keyword

Equol (EQ) Anticancer In silico In vitro In vivo 

Notes

Acknowledgments

We would like to thank Central University of Punjab, Bathinda, Punjab, (India) and Director in-charge, National Institute of Pathology, New Delhi (India) for supporting this study with infrastructural requirements. This study was also supported by a Centenary-Post Doctoral Research Fellowship Grant-in-Aid from Indian Council of Medical Research (ICMR), Government of India awarded to PS. PPK acknowledges financial support from UGC-CSIR in the form of Senior Research Fellowship.

Conflict of Interest

The authors declare that no financial or commercial conflict of interest.

References

  1. Ahmad A, Biersack B, Li Y, Bao B, Kong D, Ali S, Banerjee S, Sarkar FH. Perspectives on the role of isoflavones in prostate cancer. AAPS J. 2013;15(4):991–1000.PubMedPubMedCentralGoogle Scholar
  2. Ballester PJ. Ultrafast shape recognition: method and applications. Future Med Chem. 2011;3(1):65–78.PubMedGoogle Scholar
  3. Ballester PJ, Richards WG. Ultrafast shape recognition for similarity search in molecular databases. In: Proceedings of the Royal Society of London. Series A. Mathematical, physical and engineering sciences, vol. 2081. London: The Royal Society; 2007. p. 1307–21.Google Scholar
  4. Ballester PJ, Westwood I, Laurieri N, Sim E, Richards WG. Prospective virtual screening with ultrafast shape recognition: the identification of novel inhibitors of arylamine N-acetyltransferases. J Royal Soc Interface. 2009;7(43):335–42.Google Scholar
  5. Ballester PJ, Mangold M, Howard NI, Robinson RLM, Abell C, Blumberger J, Mitchell JB. Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification. J Royal Soc Interface. 2012;9(77):3196–207.Google Scholar
  6. Bellou S, Karali E, Bagli E, Al-Maharik N, Morbidelli L, Ziche M, Adlercreutz H, Murphy C, Fotsis T. The isoflavone metabolite 6-methoxyequol inhibits angiogenesis and suppresses tumor growth. Mol Cancer. 2012;11(35):1–11.Google Scholar
  7. Bonacasa B, Siow RC, Mann GE. Impact of dietary soy isoflavones in pregnancy on fetal programming of endothelial function in offspring. Microcirculation. 2011;18(4):270–85.PubMedGoogle Scholar
  8. Cai YF, Zhang HM, Niu WY, Zou YQ, Ma DF. Effects of equol on colon cancer cell proliferation. Beijing Da Xue Xue Bao. 2017;49(3):383–7.PubMedGoogle Scholar
  9. Charalambous C, Pitta CA, Constantinou AI. Equol enhances tamoxifen’s anti-tumor activity by induction of caspase-mediated apoptosis in MCF-7 breast cancer cells. BMC Cancer. 2013;13:238.PubMedPubMedCentralGoogle Scholar
  10. Cheong SH, Furuhashi K, Ito K, Nagaoka M, Yonezawa T, Miura Y, Yagasaki K. Antihyperglycemic effect of equol, a daidzein derivative, in cultured L6 myocytes and ob/ob mice. Mol Nutr Food Res. 2014;58(2):267–77.PubMedGoogle Scholar
  11. Cho KW, Lee OH, Banz WJ, Moustaid-Moussa N, Shay NF, Kim YC. Daidzein and the daidzein metabolite, equol, enhance adipocyte differentiation and PPARgamma transcriptional activity. J Nutr Biochem. 2010;21(9):841–7.PubMedGoogle Scholar
  12. Choi EJ. Evaluation of equol function on anti- or prooxidant status in vivo. J Food Sci. 2009;74(2):H65–71.PubMedGoogle Scholar
  13. Clubbs EA, Bomser JA. Glycitein activates extracellular signal-regulated kinase via vascular endothelial growth factor receptor signaling in nontumorigenic (RWPE-1) prostate epithelial cells. J Nutr Biochem. 2007;18(8):525–32.PubMedGoogle Scholar
  14. Dagdemir A, Durif J, Ngollo M, Bignon YJ, Bernard-Gallon D. Histone lysine trimethylation or acetylation can be modulated by phytoestrogen, estrogen or anti-HDAC in breast cancer cell lines. Epigenomics. 2013;5(1):51–63.PubMedGoogle Scholar
  15. Davinelli S, Scapagnini G, Marzatico F, Nobile V, Ferrara N, Corbi G. Influence of equol and resveratrol supplementation on health-related quality of life in menopausal women: a randomized, placebo-controlled study. Maturitas. 2017;96:77–83.PubMedGoogle Scholar
  16. de la Parra C, Borrero-Garcia LD, Cruz-Collazo A, Schneider RJ, Dharmawardhane S. Equol, an isoflavone metabolite, regulates cancer cell viability and protein synthesis initiation via c-Myc and eIF4G. J Biol Chem. 2015;290(10):6047–57.PubMedPubMedCentralGoogle Scholar
  17. Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, Repasky MP, Knoll EH, Shelley M, Perry JK. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem. 2004;47(7):1739–49.PubMedPubMedCentralGoogle Scholar
  18. Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA, Sanschagrin PC, Mainz DT. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem. 2006;49(21):6177–96.PubMedGoogle Scholar
  19. Gil-Izquierdo A, Penalvo JL, Gil JI, Medina S, Horcajada MN, Lafay S, Silberberg M, Llorach R, Zafrilla P, Garcia-Mora P, Ferreres F. Soy isoflavones and cardiovascular disease epidemiological, clinical and -omics perspectives. Curr Pharm Biotechnol. 2012;13(5):624–31.PubMedGoogle Scholar
  20. Gobert CP, Pipe EA, Capes SE, Darlington GA, Lampe JW, Duncan AM. Soya protein does not affect glycaemic control in adults with type 2 diabetes. Br J Nutr. 2010;103(3):412–21.PubMedGoogle Scholar
  21. Guadamuro L, Dohrmann AB, Tebbe CC, Mayo B, Delgado S. Bacterial communities and metabolic activity of faecal cultures from equol producer and non-producer menopausal women under treatment with soy isoflavones. BMC Microbiol. 2017;17(1):93.PubMedPubMedCentralGoogle Scholar
  22. Halgren TA, Murphy RB, Friesner RA, Beard HS, Frye LL, Pollard WT, Banks JL. Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem. 2004;47(7):1750–9.PubMedGoogle Scholar
  23. Hazim S, Curtis PJ, Schar MY, Ostertag LM, Kay CD, Minihane AM, Cassidy A. Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial. Am J Clin Nutr. 2016;103(3):694–702.PubMedPubMedCentralGoogle Scholar
  24. Hedelin M, Lof M, Sandin S, Adami HO, Weiderpass E. Prospective study of dietary phytoestrogen intake and the risk of colorectal cancer. Nutr Cancer. 2016;68(3):388–95.PubMedGoogle Scholar
  25. Hoeger B, Diether M, Ballester PJ, Köhn M. Biochemical evaluation of virtual screening methods reveals a cell-active inhibitor of the cancer-promoting phosphatases of regenerating liver. Eur J Med Chem. 2014;88:89–100.PubMedPubMedCentralGoogle Scholar
  26. Horiuchi H, Usami A, Shirai R, Harada N, Ikushiro S, Sakaki T, Nakano Y, Inui H, Yamaji R. S-Equol activates cAMP signaling at the plasma membrane of INS-1 pancreatic beta-cells and protects against streptozotocin-induced hyperglycemia by increasing beta-cell function in male mice. J Nutr. 2017;147(9):1631–9.PubMedGoogle Scholar
  27. Itsumi M, Shiota M, Takeuchi A, Kashiwagi E, Inokuchi J, Tatsugami K, Kajioka S, Uchiumi T, Naito S, Eto M. Equol inhibits prostate cancer growth through degradation of androgen receptor by S-phase kinase-associated protein 2. Cancer Sci. 2016;107(7):1022–8.PubMedPubMedCentralGoogle Scholar
  28. Jarrahpour A, Fathi J, Mimouni M, Hadda TB, Sheikh J, Chohan Z, Parvez A. Petra, Osiris and Molinspiration (POM) together as a successful support in drug design: antibacterial activity and biopharmaceutical characterization of some azo Schiff bases. Med Chem Res. 2012;21(8):1984–90.Google Scholar
  29. Jiang Y, Gong P, Madak-Erdogan Z, Martin T, Jeyakumar M, Carlson K, Khan I, Smillie TJ, Chittiboyina AG, Rotte SC, Helferich WG, Katzenellenbogen JA, Katzenellenbogen BS. Mechanisms enforcing the estrogen receptor beta selectivity of botanical estrogens. FASEB J. 2013;27(11):4406–18.PubMedPubMedCentralGoogle Scholar
  30. Jorgensen WL, Duffy EM. Prediction of drug solubility from structure. Adv Drug Deliv Rev. 2002;54(3):355–66.PubMedGoogle Scholar
  31. Jorgensen WL, Tirado-Rives J. The OPLS [optimized potentials for liquid simulations] potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin. J Am Chem Soc. 1988;110(6):1657–66.PubMedGoogle Scholar
  32. Jorgensen WL, Maxwell DS, Tirado-Rives J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J Am Chem Soc. 1996;118(45):11225–36.Google Scholar
  33. Kamiyama M, Kishimoto Y, Tani M, Utsunomiya K, Kondo K. Effects of equol on oxidized low-density lipoprotein-induced apoptosis in endothelial cells. J Atheroscler Thromb. 2009;16(3):239–49.PubMedGoogle Scholar
  34. Kartasasmita R, Musfiroh I, Muhtadi A, Ibrahim S. Binding affinity of asiatic acid derivatives design against inducible nitric oxide synthase and ADMET prediction. J Appl Pharm Sci. 2014;4(02):75–80.Google Scholar
  35. Kladna A, Berczynski P, Kruk I, Piechowska T, Aboul-Enein HY. Studies on the antioxidant properties of some phytoestrogens. Luminescence. 2016;31(6):1201–6.PubMedGoogle Scholar
  36. Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Sci World J. 2013;2013:1–16.Google Scholar
  37. Kunigal S, Lakka SS, Gondi CS, Estes N, Rao JS. RNAi-mediated downregulation of urokinase plasminogen activator receptor and matrix metalloprotease-9 in human breast cancer cells results in decreased tumor invasion, angiogenesis and growth. Int J Cancer. 2007;121(10):2307–16.PubMedPubMedCentralGoogle Scholar
  38. Landete JM, Arques J, Medina M, Gaya P, de Las Rivas B, Munoz R. Bioactivation of phytoestrogens: intestinal bacteria and health. Crit Rev Food Sci Nutr. 2016;56(11):1826–43.PubMedGoogle Scholar
  39. Li H, Leung K-S, Wong M-H, Ballester PJ. USR-VS: a web server for large-scale prospective virtual screening using ultrafast shape recognition techniques. Nucleic Acids Res. 2016;44(W1):W436–41.PubMedPubMedCentralGoogle Scholar
  40. Liang XL, Li M, Li J, Wang XL. Equol induces apoptosis in human hepatocellular carcinoma SMMC-7721 cells through the intrinsic pathway and the endoplasmic reticulum stress pathway. Anti-Cancer Drugs. 2014;25(6):633–40.PubMedGoogle Scholar
  41. Liu H, Hu C, Wu X, Li Z. Equol elicits estrogenic activities via PI3K/akt pathway in the estrogen receptor-positive MCF-7 cells. Mol Cell Toxicol. 2014;10(3):285–91.Google Scholar
  42. Liu ZM, Ho SC, Chen YM, Xie YJ, Huang ZG, Ling WH. Research protocol: effect of natural S-equol on blood pressure and vascular function – a six-month randomized controlled trial among equol non-producers of postmenopausal women with prehypertension or untreated stage 1 hypertension. BMC Complement Altern Med. 2016;16:89.PubMedPubMedCentralGoogle Scholar
  43. Liu J, Viswanadhapalli S, Garcia L, Zhou M, Nair BC, Kost E, Tekmal R, Li R, Rao MK, Curiel T, Vadlamudi RK, Sareddy GR. Therapeutic utility of natural estrogen receptor beta agonists on ovarian cancer. Oncotarget. 2017;8(30):50002–14.PubMedPubMedCentralGoogle Scholar
  44. Lu JJ, Crimin K, Goodwin JT, Crivori P, Orrenius C, Xing L, Tandler PJ, Vidmar TJ, Amore BM, Wilson AG. Influence of molecular flexibility and polar surface area metrics on oral bioavailability in the rat. J Med Chem. 2004;47(24):6104–7.PubMedGoogle Scholar
  45. Lu Z, Zhou R, Kong Y, Wang J, Xia W, Guo J, Liu J, Sun H, Liu K, Yang J, Mi M, Xu H. S-equol, a secondary metabolite of natural anticancer isoflavone daidzein, inhibits prostate cancer growth in vitro and in vivo, though activating the Akt/FOXO3a pathway. Curr Cancer Drug Targets. 2016;16(5):455–65.PubMedGoogle Scholar
  46. Magee PJ. Is equol production beneficial to health? Proc Nutr Soc. 2011;70(1):10–8.PubMedGoogle Scholar
  47. Magee PJ, Allsopp P, Samaletdin A, Rowland IR. Daidzein, R-(+) equol and S-(−) equol inhibit the invasion of MDA-MB-231 breast cancer cells potentially via the down-regulation of matrix metalloproteinase-2. Eur J Nutr. 2014;53(1):345–50.PubMedGoogle Scholar
  48. Mahmoud AM, Yang W, Bosland MC. Soy isoflavones and prostate cancer: a review of molecular mechanisms. J Steroid Biochem Mol Biol. 2014;140:116–32.PubMedGoogle Scholar
  49. Mann GE, Bonacasa B, Ishii T, Siow RC. Targeting the redox sensitive Nrf2-Keap1 defense pathway in cardiovascular disease: protection afforded by dietary isoflavones. Curr Opin Pharmacol. 2009;9(2):139–45.PubMedGoogle Scholar
  50. Miller LM, Lampe JW, Newton KM, Gundersen G, Fuller S, Reed SD, Frankenfeld CL. Being overweight or obese is associated with harboring a gut microbial community not capable of metabolizing the soy isoflavone daidzein to O-desmethylangolensin in peri- and post-menopausal women. Maturitas. 2017;99:37–42.PubMedGoogle Scholar
  51. Minakawa M, Kawano A, Miura Y, Yagasaki K. Hypoglycemic effect of resveratrol in type 2 diabetic model db/db mice and its actions in cultured L6 myotubes and RIN-5F pancreatic β-cells. J Clin Biochem Nutr. 2011;48(3):237–44.PubMedPubMedCentralGoogle Scholar
  52. Miyanaga N, Akaza H. Prostate cancer prevention. Gan to kagaku ryoho Cancer Chemother. 2015;42(5):538–43.Google Scholar
  53. Muster W, Breidenbach A, Fischer H, Kirchner S, Müller L, Pähler A. Computational toxicology in drug development. Drug Discov Today. 2008;13(7):303–10.PubMedGoogle Scholar
  54. Obiorah IE, Fan P, Jordan VC. Breast cancer cell apoptosis with phytoestrogens is dependent on an estrogen-deprived state. Cancer Prev Res. 2014;7(9):939–49.Google Scholar
  55. Ono M, Ejima K, Higuchi T, Takeshima M, Wakimoto R, Nakano S. Equol enhances apoptosis-inducing activity of genistein by increasing Bax/Bcl-xL expression ratio in MCF-7 human breast cancer cells. Nutr Cancer. 2017;69(8):1300–7.PubMedGoogle Scholar
  56. Patil SP, Ballester PJ, Kerezsi CR. Prospective virtual screening for novel p53–MDM2 inhibitors using ultrafast shape recognition. J Comput Aided Mol Des. 2014;28(2):89–97.PubMedGoogle Scholar
  57. Patisaul HB. Endocrine disruption by dietary phyto-oestrogens: impact on dimorphic sexual systems and behaviours. Proc Nutr Soc. 2017;76(2):130–44.PubMedGoogle Scholar
  58. Pawlowski JW, Martin BR, McCabe GP, McCabe L, Jackson GS, Peacock M, Barnes S, Weaver CM. Impact of equol-producing capacity and soy-isoflavone profiles of supplements on bone calcium retention in postmenopausal women: a randomized crossover trial. Am J Clin Nutr. 2015;102(3):695–703.PubMedPubMedCentralGoogle Scholar
  59. Pazourekova S, Lucova M, Nosal R, Drabikova K, Harmatha J, Smidrkal J, Jancinova V. Equol effectively inhibits toxic activity of human neutrophils without influencing their viability. Pharmacology. 2016;97(3–4):138–45.PubMedGoogle Scholar
  60. Reverri EJ, LaSalle CD, Franke AA, Steinberg FM. Soy provides modest benefits on endothelial function without affecting inflammatory biomarkers in adults at cardiometabolic risk. Mol Nutr Food Res. 2015;59(2):323–33.PubMedGoogle Scholar
  61. Richter CK, Skulas-Ray AC, Fleming JA, Link CJ, Mukherjea R, Krul ES, Kris-Etherton PM. Effects of isoflavone-containing soya protein on ex vivo cholesterol efflux, vascular function and blood markers of CVD risk in adults with moderately elevated blood pressure: a dose-response randomised controlled trial. Br J Nutr. 2017;117(10):1403–13.PubMedPubMedCentralGoogle Scholar
  62. Rigalli JP, Scholz PN, Tocchetti GN, Ruiz ML, Weiss J. The phytoestrogens daidzein and equol inhibit the drug transporter BCRP/ABCG2 in breast cancer cells: potential chemosensitizing effect. Eur J Nutr. 2017;58(1):39–150.Google Scholar
  63. Sakane N, Kotani K, Tsuzaki K, Takahashi K, Usui T, Uchiyama S, Fujiwara S. Equol producers can have low leptin levels among prediabetic and diabetic females. Ann Endocrinol. 2014;75(1):25–8.Google Scholar
  64. Sareddy GR, Vadlamudi RK. Cancer therapy using natural ligands that target estrogen receptor beta. Chin J Nat Med. 2015;13(11):801–7.PubMedPubMedCentralGoogle Scholar
  65. Schreyer AM, Blundell T. USRCAT: real-time ultrafast shape recognition with pharmacophoric constraints. J Cheminform. 2012;4(1):27.PubMedPubMedCentralGoogle Scholar
  66. Setchell KD, Clerici C. Equol: history, chemistry, and formation. J Nutr. 2010;140(7):1355s–62s.PubMedPubMedCentralGoogle Scholar
  67. Sharma M, Lawson J, Karunanayake C, Dosman J, Punam P. Prostate cancer, farming and other risk factors: a mini review. J Pros Canc. 2016;1(109):2.Google Scholar
  68. Shivakumar D, Williams J, Wu Y, Damm W, Shelley J, Sherman W. Prediction of absolute solvation free energies using molecular dynamics free energy perturbation and the OPLS force field. J Chem Theory Comput. 2010;6(5):1509–19.PubMedGoogle Scholar
  69. Singh P, Bast F. In silico molecular docking study of natural compounds on wild and mutated epidermal growth factor receptor. Med Chem Res. 2014a;23(12):5074–85.Google Scholar
  70. Singh P, Bast F. Multitargeted molecular docking study of plant-derived natural products on phosphoinositide-3 kinase pathway components. Med Chem Res. 2014b;23(4):1690–700.Google Scholar
  71. Singh P, Bast F. Screening and biological evaluation of myricetin as a multiple target inhibitor insulin, epidermal growth factor, and androgen receptor; in silico and in vitro. Investig New Drugs. 2015a;33(3):575–93.Google Scholar
  72. Singh P, Bast F. Screening of multi-targeted natural compounds for receptor tyrosine kinases inhibitors and biological evaluation on cancer cell lines, in silico and in vitro. Med Oncol. 2015b;32(9):1–18.Google Scholar
  73. Singh P, Singh RS, Rani A, Bast F. Homology modeling of chemokine CCR7, molecular docking, and in vitro studies evidenced plausible immunotherapeutic anticancer natural compounds. Med Chem Res. 2016;25(10):2410–24.Google Scholar
  74. Son MJ, Minakawa M, Miura Y, Yagasaki K. Aspalathin improves hyperglycemia and glucose intolerance in obese diabetic ob/ob mice. Eur J Nutr. 2013;52(6):1607–19.PubMedGoogle Scholar
  75. Subedi L, Ji E, Shin D, Jin J, Yeo JH, Kim SY. Equol, a dietary daidzein gut metabolite attenuates microglial activation and potentiates neuroprotection in vitro. Nutrients. 2017;9(3):207.PubMedCentralGoogle Scholar
  76. Sugiyama Y, Masumori N, Fukuta F, Yoneta A, Hida T, Yamashita T, Minatoya M, Nagata Y, Mori M, Tsuji H, Akaza H, Tsukamoto T. Influence of isoflavone intake and equol-producing intestinal flora on prostate cancer risk. Asian Pac J Cancer Prev. 2013;14(1):1–4.PubMedGoogle Scholar
  77. Taghizadeh B, Ghavami L, Nikoofar A, Goliaei B. Equol as a potent radiosensitizer in estrogen receptor-positive and -negative human breast cancer cell lines. Breast Cancer. 2015;22(4):382–90.PubMedGoogle Scholar
  78. Tanaka M, Fujimoto K, Chihara Y, Torimoto K, Yoneda T, Tanaka N, Hirayama A, Miyanaga N, Akaza H, Hirao Y. Isoflavone supplements stimulated the production of serum equol and decreased the serum dihydrotestosterone levels in healthy male volunteers. Prostate Cancer Prostatic Dis. 2009;12(3):247.PubMedPubMedCentralGoogle Scholar
  79. Tseng M, Byrne C, Kurzer MS, Fang CY. Equol-producing status, isoflavone intake, and breast density in a sample of U.S. Chinese women. Cancer Epidemiol Biomarkers Prev: Publ Am Assoc Cancer Res. 2013;22(11):1975–83.Google Scholar
  80. Uehara M. Isoflavone metabolism and bone-sparing effects of daidzein-metabolites. J Clin Biochem Nutr. 2013;52(3):193–201.PubMedPubMedCentralGoogle Scholar
  81. Vafeiadou K, Hall WL, Williams CM. Does genotype and equol-production status affect response to isoflavones? Data from a pan-European study on the effects of isoflavones on cardiovascular risk markers in post-menopausal women. Proc Nutr Soc. 2006;65(1):106–15.PubMedGoogle Scholar
  82. Vazquez L, Guadamuro L, Giganto F, Mayo B, Florez AB. Development and use of a real-time quantitative PCR method for detecting and quantifying equol-producing bacteria in human faecal samples and slurry cultures. Front Microbiol. 2017;8:1155.PubMedPubMedCentralGoogle Scholar
  83. Vedavanam K, Srijayanta S, O’Reilly J, Raman A, Wiseman H. Antioxidant action and potential antidiabetic properties of an isoflavonoid-containing soyabean phytochemical extract (SPE). Phytother Res. 1999;13(7):601–8.PubMedGoogle Scholar
  84. Vimal A, Pal D, Tripathi T, Kumar A. Eucalyptol, sabinene and cinnamaldehyde: potent inhibitors of salmonella target protein L-asparaginase. 3 Biotech. 2017;7(4):258.PubMedPubMedCentralGoogle Scholar
  85. Virk-Baker MK, Barnes S, Krontiras H, Nagy TR. S-(−) equol producing status not associated with breast cancer risk among low isoflavone-consuming US postmenopausal women undergoing a physician-recommended breast biopsy. Nutr Res. 2014;34(2):116–25.PubMedGoogle Scholar
  86. Wang M, Ren G. Study on the inhibiting effects of equol on MCF-7 cells proliferation and its molecular mechanisms. J Hyg Res. 2014;43(1):11–5.Google Scholar
  87. Yang X, Belosay A, Hartman JA, Song H, Zhang Y, Wang W, Doerge DR, Helferich WG. Dietary soy isoflavones increase metastasis to lungs in an experimental model of breast cancer with bone micro-tumors. Clin Exp Metastasis. 2015a;32(4):323–33.PubMedPubMedCentralGoogle Scholar
  88. Yang ZP, Zhao Y, Huang F, Chen J, Yao YH, Li J, Wu XN. Equol inhibits proliferation of human gastric carcinoma cells via modulating Akt pathway. World J Gastroenterol. 2015b;21(36):10385–99.PubMedPubMedCentralGoogle Scholar
  89. Yang Z, Zhao Y, Yao Y, Li J, Wang W, Wu X. Equol induces mitochondria-dependent apoptosis in human gastric cancer cells via the sustained activation of ERK1/2 pathway. Mol Cell. 2016;39(10):742–9.Google Scholar
  90. Yoshikata R, Myint KZ, Ohta H. Relationship between equol producer status and metabolic parameters in 743 Japanese women: equol producer status is associated with antiatherosclerotic conditions in women around menopause and early postmenopause. Menopause. 2017;24(2):216–24.PubMedGoogle Scholar
  91. Zhang T, Liang X, Shi L, Wang L, Chen J, Kang C, Zhu J, Mi M. Estrogen receptor and PI3K/Akt signaling pathway involvement in S-(−) equol-induced activation of Nrf2/ARE in endothelial cells. PLoS One. 2013;8(11):e79075.PubMedPubMedCentralGoogle Scholar
  92. Zhang Q, Feng H, Qluwakemi B, Wang J, Yao S, Cheng G, Xu H, Qiu H, Zhu L, Yuan M. Phytoestrogens and risk of prostate cancer: an updated meta-analysis of epidemiologic studies. Int J Food Sci Nutr. 2017;68(1):28–42.PubMedGoogle Scholar
  93. Zheng W, Zhang Y, Ma D, Shi Y, Liu C, Wang P. (+/−) Equol inhibits invasion in prostate cancer DU145 cells possibly via down-regulation of matrix metalloproteinase-9, matrix metalloproteinase-2 and urokinase-type plasminogen activator by antioxidant activity. J Clin Biochem Nutr. 2012;51(1):61–7.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Pushpendra Singh
    • 1
  • Prem P. Kushwaha
    • 2
  • Shashank Kumar
    • 2
  1. 1.Tumor Biology LaboratoryNational Institute of PathologyNew DelhiIndia
  2. 2.Department of Biochemistry and Microbial SciencesCentral University of PunjabBathindaIndia

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