Absorption, Metabolism, and Disposition of Flavonoids and Their Role in the Prevention of Distinctive Cancer Types

  • Siddhi Bagwe-Parab
  • Ginpreet Kaur
  • Harpal Singh Buttar
  • Hardeep Singh Tuli


Flavonoids consist of a large family of polyphenolic molecules like flavones, flavonols, flavanols, isoflavones, flavanones, and anthocyanidins which are ubiquitously distributed in nature and are present in a wide array of plant products, including fruits, vegetables, and green tea. Because of their powerful antioxidant, anti-inflammatory, and anticancer properties, rigorous research is going on with a number of flavonoids (quercetin, quercitrin, rutin, morin, kaempferol, etc.) to investigate their disease-preventive and health-promoting benefits in humans. Several studies have shown that the cancer prevention and pharmacotherapeutic potential of different flavonoids depend on the type of flavonoid and its chemical structure, bioavailability, effective blood levels, and pharmacokinetic and pharmacodynamic characteristics. Many in vivo and in vitro studies conducted with different types of flavonoids have revealed diverse effects against different types of cancers. However, the major flavonoids (apigenin, luteolin, kaempferol) found in vegetarian diet have depicted limited possibility of curing cancer. In vitro studies done with apigenin and luteolin have shown effectiveness against cervical cancer cells, while kaempferol produced oncolytic effects against gastric and ovarian cancer cells. These flavonoids and their metabolites have revealed different anticancer effects due to their rapid metabolism in the small intestine and liver. Cancers comprise a group of noncommunicable diseases characterized by long-term debilitating illnesses that cause heavy burden on the healthcare system. At present, certain types of cancers are incurable, and palliative interventions are directed to delay the spread of malignant cancer and to ameliorate the painful episodes associated with cancer. The purpose of this review is to focus on the absorption, distribution, metabolism, and excretion (ADME) of different flavonoids and to evaluate the immune-boosting, cancer-preventive, and therapeutic potential of flavonoids against different types of cancers.


Flavonoids Oxidative stress Antioxidant Anti-inflammation Anticancer Cancer prevention Chemoprotection ADME 


Conflict of Interest

The authors declare no conflict of interest.


  1. Ananga A, Obuya J, Ochieng J et al (2017) Grape seed nutraceuticals for disease prevention: current status and future prospects. In: Phenolic compounds-biological activity. InTech, LondonGoogle Scholar
  2. Androutsopoulos VP, Spandidos DA (2013) The flavonoids diosmetin and luteolin exert synergistic cytostatic effects in human hepatoma HepG2 cells via CYP1A-catalyzed metabolism, activation of JNK and ERK and P53/P21 up-regulation. J Nutr Biochem 24:496–504CrossRefGoogle Scholar
  3. Baba S, Furuta T, Fujioka M et al (1983) Studies on drug metabolism by use of isotopes XXVII: urinary metabolites of rutin in rats and the role of intestinal microflora in the metabolism of rutin. J Pharm Sci 72:1155–1158CrossRefGoogle Scholar
  4. Beydokthi SS, Sendker J, Brandt S et al (2017) Traditionally used medicinal plants against uncomplicated urinary tract infections: Hexadecyl coumaric acid ester from the rhizomes of Agropyron repens (L.) P. Beauv. With antiadhesive activity against uropathogenic E. coli. Fitoterapia 117:22–27CrossRefGoogle Scholar
  5. Bilyk A, Sapers GM (1985) Distribution of quercetin and kaempferol in lettuce, kale, chive, garlic chive, leek, horseradish, red radish, and red cabbage tissues. J Agric Food Chem 33:226–228CrossRefGoogle Scholar
  6. Brouillard R, Cheminant A (1988) Flavonoids and plant color. In: Cody V, Middleton E, Harborne JB (eds) Plant flavonoids in biology and medicine: biochemical, cellular and medicinal properties. Alan R. Liss, Inc., New York, pp 93–106Google Scholar
  7. Bulzomi P, Bolli A, Galluzo P et al (2012) The naringenin-induced proapoptotic effect in breast cancer cell lines holds out against a high bisphenol a background. IUBMB Life 64:690–696CrossRefGoogle Scholar
  8. Cermak R, Landgraf S, Wolffram S (2004) Quercetin glucosides inhibit glucose uptake into brush-border-membrane vesicles of porcine jejunum. Br J Nutr 91:849–855CrossRefGoogle Scholar
  9. Chien CS, Shen KH, Huang JS et al (2010) Antimetastatic potential of fisetin involves inactivation of the PI3K/Akt and JNK signaling pathways with downregulation of MMP-2/9 expressions in prostate cancer PC-3 cells. Mol Cell Biochem 333:169CrossRefGoogle Scholar
  10. Cody V, Middleton E, Harborne JB (1986) Plant flavonoids in biology and medicine: biochemical, pharmacological, and structure-activity relationships. Prog Clin Biol Res 213:1–592Google Scholar
  11. Cook NC, Samman S (1996) Flavonoids–chemistry, metabolism, cardioprotective effects, and dietary sources. J Nutr Biochem 7:66–76CrossRefGoogle Scholar
  12. Cummings JH, Macfarlane GT (1991) The control and consequences of bacterial fermentation in the human colon. J Appl Bacteriol 70:443–459CrossRefGoogle Scholar
  13. Dai Z, Nair V, Khan M et al (2010) Pomegranate extract inhibits the proliferation and viability of MMTV-Wnt-1 mouse mammary cancer stem cells in vitro. Oncol Rep 24:1087–1091PubMedGoogle Scholar
  14. Daniels LB, Coyle PJ, Chiao YB et al (1981) Purification and characterization of a cytosolic broad specificity beta-glucosidase from human liver. J Biol Chem 256:13004–13013PubMedGoogle Scholar
  15. Day AJ, Cañada FJ, Díaz JC et al (2000) Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett 468:166–170CrossRefGoogle Scholar
  16. Déprez S, Mila I, Scalbert A (1999) Carbon-14 biolabeling of (+)-catechin and proanthocyanidin oligomers in willow tree cuttings. J Agric Food Chem 47:4219–4230CrossRefGoogle Scholar
  17. Doostdar H, Burke MD, Mayer RT (2000) Bioflavonoids: selective substrates and inhibitors for cytochrome P450 CYP1A and CYP1B1. Toxicology 144:31–38CrossRefGoogle Scholar
  18. Eckberg WR, Perotti ME (1983) Inhibition of gamete membrane fusion in the sea urchin by quercetin. Biol Bull 164:62–70CrossRefGoogle Scholar
  19. Erlund I, Alfthan G, Mäenpää J et al (2001) Tea and coronary heart disease: the flavonoid quercetin is more bioavailable from rutin in women than in men. Arch Intern Med 161:1919–1920CrossRefGoogle Scholar
  20. Farkas L, Gabor M, Kallay F (1986) Flavonoids and bioflavonoids. Akademiai Kiado, BudapestGoogle Scholar
  21. Gabor M (1986) The pharmacology of benzopyrone derivatives and related compounds. Akademiai Kiad, BudapestGoogle Scholar
  22. Gee JM, DuPont MS, Rhodes MJ et al (1998) Quercetin glucosides interact with the intestinal glucose transport pathway 1. Free Radic Biol Med 25:19–25CrossRefGoogle Scholar
  23. Gibellini L, Pinti M, Nasi M et al (2011) Quercetin and cancer chemoprevention. Evid Based Complement Alternat Med 2011:591356CrossRefGoogle Scholar
  24. Gopalan VE, Pastuszyn A, Galey WR et al (1992) Exolytic hydrolysis of toxic plant glucosides by Guinea pig liver cytosolic beta-glucosidase. J Biol Chem 267:14027–14032PubMedGoogle Scholar
  25. Griffiths LA, Barrow A (1972) The fate of orally and parenterally administered flavonoids in the mammal. Angiologica 9:162–174PubMedGoogle Scholar
  26. Griffiths K, Aggarwal BB, Singh RB et al (2016) Food antioxidants and their anti-inflammatory properties: a potential role in cardiovascular diseases and cancer prevention. Diseases 4:28CrossRefGoogle Scholar
  27. Groenewoud G, Hundt HKL (1986) The microbial metabolism of condensed (+)-catechins by rat-caecal microflora. Xenobiotica 16:99–107CrossRefGoogle Scholar
  28. Gullón B, Lú-Chau TA, Moreira MT et al (2017) Rutin: a review on extraction, identification and purification methods, biological activities and approaches to enhance its bioavailability. Trends Food Sci Technol 67:220–235CrossRefGoogle Scholar
  29. Hackett AM (1986) The metabolism of flavonoid compounds in mammals. Prog Clin Biol Res 213:177PubMedGoogle Scholar
  30. Hallman K, Aleck K, Quigley M et al (2017) The regulation of steroid receptors by epigallocatechin-3-gallate in breast cancer cells. Breast Cancer (Dove Med Press) 9:365Google Scholar
  31. Hammerstone JF, Lazarus SA, Schmitz HH (2000) Procyanidin content and variation in some commonly consumed foods. J Nutr 130:2086S–2092SCrossRefGoogle Scholar
  32. Havsteen B (1984) Flavonoids: a class of natural products of high pharmacological potency. Biochem Pharmacol 32:1141–1148CrossRefGoogle Scholar
  33. Hertog MGL, Hollman PCH, Katan MB (1992) Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in the Netherlands. J Agric Food Chem 40:2379–2383CrossRefGoogle Scholar
  34. Hertog MG, Hollman PC, Katan MB et al (1993) Intake of potentially anticarcinogenic flavonoids and their determinants in adults in the Netherlands. Nutr Cancer 20:21–29CrossRefGoogle Scholar
  35. Hollman PC, Katan MB (1998) Bioavailability and health effects of dietary flavonols in man. Arch Toxicol Suppl 20:237–248CrossRefGoogle Scholar
  36. Hollman PH, Katan MB (1999) Dietary flavonoids: intake, health effects and bioavailability. Food Chem Toxicol 37:937–942CrossRefGoogle Scholar
  37. Hollman PC, Bijsman MN, van Gameren Y et al (1999) The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radic Res 31:569–573CrossRefGoogle Scholar
  38. Hostetler GL, Ralston RA, Schwartz SJ (2017) Flavones: food sources, bioavailability, metabolism, and bioactivity. Adv Nutr 8:423–435CrossRefGoogle Scholar
  39. Kefford JF, Chandler BV (eds) (1970) The chemical constituents of citrus fruits. Academic Press, New YorkGoogle Scholar
  40. Kinjo J, Nagao T, Tanaka T et al (2002) Activity-guided fractionation of green tea extract with antiproliferative activity against human stomach cancer cells. Biol Pharm Bull 25:1238–1240CrossRefGoogle Scholar
  41. Knekt P, Isotupa S, Rissanen H et al (2000) Quercetin intake and the incidence of cerebrovascular disease. Eur J Clin Nutr 54:415CrossRefGoogle Scholar
  42. Křížková J, Burdová K, Stiborová M et al (2009) The effects of selected flavonoids on cytochromes P450 in rat liver and small intestine. Interdiscip Toxicol 2:201–204CrossRefGoogle Scholar
  43. Leese HJ, Semenza G (1973) On the identity between the small intestinal enzymes phlorizin hydrolase and glycosylceramidase. J Biol Chem 248:8170–8173PubMedGoogle Scholar
  44. Levy R, Faber KA, Ayyash L et al (1995) The effect of prenatal exposure to the phytoestrogen genistein on sexual differentiation in rats. Proc Soc Exp Biol Med 208:60–66CrossRefGoogle Scholar
  45. Liao S, Umekita Y, Guo J et al (1995) Growth inhibition and regression of human prostate and breast tumors in athymic mice by tea epigallocatechin gallate. Cancer Lett 96:239–243CrossRefGoogle Scholar
  46. Moon JH, Nakata R, Oshima S et al (2000) Accumulation of quercetin conjugates in blood plasma after the short-term ingestion of onion by women. Am J Phys Regul Integr Comp Phys 279:R461–R467Google Scholar
  47. Morales P, Haza AI (2012) Selective apoptotic effects of piceatannol and myricetin in human cancer cells. J Appl Toxicol 32:986–993CrossRefGoogle Scholar
  48. Mukherjee S, Debata PR, Hussaini R et al (2017) Unique synergistic formulation of curcumin, epicatechin gallate and resveratrol, tricurin, suppresses HPV E6, eliminates HPV+ cancer cells, and inhibits tumor progression. Oncotarget 8:60904PubMedPubMedCentralGoogle Scholar
  49. Murota K, Shimizu S, Miyamoto S et al (2002) Unique uptake and transport of isoflavone aglycones by human intestinal Caco-2 cells: comparison of isoflavonoids and flavonoids. J Nutr 132:1956–1961CrossRefGoogle Scholar
  50. Nass-Arden L, Breitbart H (1990) Modulation of mammalian sperm motility by quercetin. Mol Reprod Dev 25:369–373CrossRefGoogle Scholar
  51. Olthof MR, Hollman PC, Vree TB et al (2000) Bioavailabilities of quercetin-3-glucoside and quercetin-4′-glucoside do not differ in humans. J Nutr 130:1200–1203CrossRefGoogle Scholar
  52. Olthof MR, Hollman PC, Buijsman MN et al (2003) Chlorogenic acid, quercetin-3-rutinoside and black tea phenols are extensively metabolized in humans. J Nutr 133:1806–1814CrossRefGoogle Scholar
  53. Passamonti S, Terdoslavich M, Franca R et al (2009) Bioavailability of flavonoids: a review of their membrane transport and the function of bilitranslocase in animal and plant organisms. Curr Drug Metab 10:369–394CrossRefGoogle Scholar
  54. Rice-Evans CA, Packer L (eds) (1998) Flavonoids in health and disease. Marcel Dekker, Inc., New YorkGoogle Scholar
  55. Sato F, Matsukawa Y, Matsumoto K et al (1994) Apigenin induces morphological differentiation and G2-M arrest in rat neuronal cells. Biochem Biophys Res Commun 204:578–584CrossRefGoogle Scholar
  56. Scheline RR (1991) Handbook of mammalian metabolism of plant compounds. CRC Press, Boca RatonGoogle Scholar
  57. Semwal DK, Semwal RB, Combrinck S et al (2016) Myricetin: a dietary molecule with diverse biological activities. Nutrients 8:90CrossRefGoogle Scholar
  58. Spencer JP, Chaudry F, Pannala AS et al (2000) Decomposition of cocoa procyanidins in the gastric milieu. Biochem Biophys Res Commun 272:236–241CrossRefGoogle Scholar
  59. Strouch MJ, Milam BM, Melstrom LG et al (2009) The flavonoid apigenin potentiates the growth inhibitory effects of gemcitabine and abrogates gemcitabine resistance in human pancreatic cancer cells. Pancreas 38:409–415CrossRefGoogle Scholar
  60. Swain T (1975) Evolution of flavonoid compounds. In: Harborne JB, Mabry TJ, Mabry H (eds) The flavonoids. Chapman and Hall, Ltd., London, pp 109–1129Google Scholar
  61. Terao J, Kawai Y, Murota K (2008) Vegetable flavonoids and cardiovascular disease. Asia Pac J Clin Nutr 17:291–293PubMedGoogle Scholar
  62. Truong HH, Neilson KA, McInerney BV et al (2017) Comparative performance of broiler chickens offered nutritionally equivalent diets based on six diverse, ‘tannin-free’sorghum varieties with quantified concentrations of phenolic compounds, kafirin, and phytate. Anim Prod Sci 57:828–838CrossRefGoogle Scholar
  63. Welton AR, Hurley I, Will P (1988) Flavonoids and arachidonic acid metabolism. In: Cody V, Middleton E, Harborne JB, Beretz A (eds) Plant flavonoids in biology and medicine II: biochemical, cellular and medicinal properties. Alan R. Liss, Inc., New York, pp 301–312Google Scholar
  64. Winter J, Popoff MR, Grimont P et al (1991) Clostridium orbiscindens sp. nov., a human intestinal bacterium capable of cleaving the flavonoid C-ring. Int J Syst Evol Microbiol 41:355–357Google Scholar
  65. Xiang L-P et al (2016) Suppressive effects of tea catechins on breast cancer. Nutrients 8(8):458CrossRefGoogle Scholar
  66. Yin F, Giuliano AE, Law RE et al (2001) Apigenin inhibits growth and induces G2/M arrest by modulating cyclin-CDK regulators and ERK MAP kinase activation in breast carcinoma cells. Anticancer Res 21:413–420PubMedGoogle Scholar
  67. Yu C, Jiao Y, Xue J et al (2017) Metformin sensitizes non-small cell lung cancer cells to an epigallocatechin-3-gallate (EGCG) treatment by suppressing the Nrf2/HO-1 signaling pathway. Int J Biol Sci 13:1560–1569CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Siddhi Bagwe-Parab
    • 1
  • Ginpreet Kaur
    • 1
  • Harpal Singh Buttar
    • 2
  • Hardeep Singh Tuli
    • 3
  1. 1.Department of PharmacologySPP School of Pharmacy and Technology ManagementMumbaiIndia
  2. 2.Department of Pathology and Laboratory Medicine, Faculty of MedicineUniversity of OttawaOttawaCanada
  3. 3.Department of BiotechnologyMaharishi Markandeshwar (Deemed to be University)Mullana-AmbalaIndia

Personalised recommendations