Molecular Biotechnology

, Volume 55, Issue 1, pp 78–86

Potential Role of Naturally Derived Polyphenols and Their Nanotechnology Delivery in Cancer



Polyphenols are natural compounds found in plants, fruits, chocolate, and beverages such as tea and wine. To date, the majority of polyphenol research shows them to have anticancer activity in cell lines and animal models. Some human clinical trials also indicate possible anticancer benefits are associated with polyphenols. A problem with polyphenols is their short half-life and low bioavailability; thus the use of nanoparticles to enhance their delivery is a new research field. A Pubmed search was conducted to find in vitro, in vivo, and human clinical trials done within the past 10 years involving the use of polyphenols against different cancer types, and for studies done within the past 5 years on the use of nanoparticles to enhance polyphenol delivery. Based on the studies found, it is observed that polyphenols may be a potential alternative or additive therapy against cancer, and the use of nanoparticles to enhance their delivery to tumors is a promising approach. However, further human clinical trials are necessary to better understand the use of polyphenols as well as their nanoparticle-mediated delivery.


Polyphenol Cancer Experimental cancer models Natural products Anticancer Nanotechnology Nanoformulation Pharmacokinetic Pharmacodynamic 


  1. 1.
    National Cancer Institute. Surveillance epidemiology and end sites. Retrieved July 26, 2012, from
  2. 2.
    Scalbert, A., Manach, C., Morand, C., Remesy, C., & Jimenez, L. (2005). Dietary polyphenols and the prevention of diseases. Critical Reviews in Food Science and Nutrition, 45, 287–306.CrossRefGoogle Scholar
  3. 3.
    Bravo, L. (1998). Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance. Nutrition Reviews, 56, 317–333.CrossRefGoogle Scholar
  4. 4.
    Quideau, S., Deffieux, D., Douat-Casassus, C., & Pouysegu, L. (2011). Plant polyphenols: Chemical properties, biological activities, and synthesis. Angewandte Chemie (International ed. in English), 50, 586–621. doi:10.1002/anie.201000044.CrossRefGoogle Scholar
  5. 5.
    Crozier, A., Jaganath, I. B., & Clifford, M. N. (2009). Dietary phenolics: Chemistry, bioavailability and effects on health. Natural Products Reports, 26, 1001–1043. doi:10.1039/b802662a.CrossRefGoogle Scholar
  6. 6.
    Amorati, R., & Valgimigli, L. (2012). Modulation of the antioxidant activity of phenols by non-covalent interactions. Organic & Biomolecular Chemistry, 10, 4147–4158. doi:10.1039/c2ob25174d.CrossRefGoogle Scholar
  7. 7.
    Weseler, A. R., Ruijters, E. J., Drittij-Reijnders, M. J., Reesink, K. D., Haenen, G. R., & Bast, A. (2011). Pleiotropic benefit of monomeric and oligomeric flavanols on vascular health—A randomized controlled clinical pilot study. PLoS ONE, 6, e28460. doi:10.1371/journal.pone.0028460.CrossRefGoogle Scholar
  8. 8.
    Arts, I. C., & Hollman, P. C. (2005). Polyphenols and disease risk in epidemiologic studies. American Journal of Clinical Nutrition, 81, 317S–325S.Google Scholar
  9. 9.
    Johnson, I. T., Williamson, G., & Musk, S. R. (1994). Anticarcinogenic factors in plant foods: A new class of nutrients? Nutrition Research Reviews, 7, 175–204. doi:10.1079/NRR19940011.CrossRefGoogle Scholar
  10. 10.
    Agullo, G., Gamet-Payrastre, L., Fernandez, Y., Anciaux, N., Demigne, C., & Remesy, C. (1996). Comparative effects of flavonoids on the growth, viability and metabolism of a colonic adenocarcinoma cell line (HT29 cells). Cancer Letters, 105, 61–70.CrossRefGoogle Scholar
  11. 11.
    Kuntz, S., Wenzel, U., & Daniel, H. (1999). Comparative analysis of the effects of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines. European Journal of Nutrition, 38, 133–142.CrossRefGoogle Scholar
  12. 12.
    Dong, Z., Ma, W., Huang, C., & Yang, C. S. (1997). Inhibition of tumor promoter-induced activator protein 1 activation and cell transformation by tea polyphenols, (−)-epigallocatechin gallate, and theaflavins. Cancer Research, 57, 4414–4419.Google Scholar
  13. 13.
    Barthelman, M., Bair, W. B., 3rd, Stickland, K. K., Chen, W., Timmermann, B. N., Valcic, S., et al. (1998). (−)-Epigallocatechin-3-gallate inhibition of ultraviolet B-induced AP-1 activity. Carcinogenesis, 19, 2201–2204.CrossRefGoogle Scholar
  14. 14.
    Linsalata, M., Orlando, A., Messa, C., Refolo, M. G., & Russo, F. (2010). Quercetin inhibits human DLD-1 colon cancer cell growth and polyamine biosynthesis. Anticancer Research, 30, 3501–3507.Google Scholar
  15. 15.
    National Cancer Institute. Antioxidants and cancer prevention: Fact sheet. Retrieved July 27, 2012, from
  16. 16.
    Boocock, D. J., Patel, K. R., Faust, G. E., Normolle, D. P., Marczylo, T. H., Crowell, J. A., et al. (2007). Quantitation of trans-resveratrol and detection of its metabolites in human plasma and urine by high performance liquid chromatography. Journal of Chromatography B: Analytical Technology in the Biomedical and Life Sciences, 848, 182–187. doi:10.1016/j.jchromb.2006.10.017.CrossRefGoogle Scholar
  17. 17.
    Anand, P., Kunnumakkara, A. B., Newman, R. A., & Aggarwal, B. B. (2007). Bioavailability of curcumin: Problems and promises. Molecular Pharmaceutics, 4, 807–818. doi:10.1021/mp700113r.CrossRefGoogle Scholar
  18. 18.
    Siddiqui, I. A., Adhami, V. M., Bharali, D. J., Hafeez, B. B., Asim, M., Khwaja, S. I., et al. (2009). Introducing nanochemoprevention as a novel approach for cancer control: Proof of principle with green tea polyphenol epigallocatechin-3-gallate. Cancer Research, 69, 1712–1716. doi:10.1158/0008-5472.CAN-08-3978.CrossRefGoogle Scholar
  19. 19.
    Gref, R., Minamitake, Y., Peracchia, M. T., Trubetskoy, V., Torchilin, V., & Langer, R. (1994). Biodegradable long-circulating polymeric nanospheres. Science, 263, 1600–1603.CrossRefGoogle Scholar
  20. 20.
    Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., & Langer, R. (2007). Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnology, 2, 751–760. doi:10.1038/nnano.2007.387.CrossRefGoogle Scholar
  21. 21.
    Rocha, S., Generalov, R., Pereira Mdo, C., Peres, I., Juzenas, P., & Coelho, M. A. (2011). Epigallocatechin gallate-loaded polysaccharide nanoparticles for prostate cancer chemoprevention. Nanomedicine (London), 6, 79–87. doi:10.2217/nnm.10.101.CrossRefGoogle Scholar
  22. 22.
    Centers for Disease Control and Prevention. (2011). Colorectal (colon) cancer. Retrieved July 27, 2012, from
  23. 23.
    White, E., Jacobs, E. J., & Daling, J. R. (1996). Physical activity in relation to colon cancer in middle-aged men and women. American Journal of Epidemiology, 144, 42–50.CrossRefGoogle Scholar
  24. 24.
    Calle, E. E., Rodriguez, C., Walker-Thurmond, K., & Thun, M. J. (2003). Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. New England Journal of Medicine, 348, 1625–1638. doi:10.1056/NEJMoa021423.CrossRefGoogle Scholar
  25. 25.
    Martinez, M. E., Giovannucci, E., Spiegelman, D., Hunter, D. J., Willett, W. C., & Colditz, G. A. (1997). Leisure-time physical activity, body size, and colon cancer in women. Nurses’ Health Study Research Group. Journal of the National Cancer Institute, 89, 948–955.CrossRefGoogle Scholar
  26. 26.
    Cho, E., Smith-Warner, S. A., Ritz, J., van den Brandt, P. A., Colditz, G. A., Folsom, A. R., et al. (2004). Alcohol intake and colorectal cancer: A pooled analysis of 8 cohort studies. Annals of Internal Medicine, 140, 603–613.CrossRefGoogle Scholar
  27. 27.
    Reddy, B. S., Hedges, A., Laakso, K., & Wynder, E. L. (1978). Fecal constituents of a high-risk North American and a low-risk Finnish population for the development of large bowel cancer. Cancer Letters, 4, 217–222.CrossRefGoogle Scholar
  28. 28.
    Neugut, A. I., Jacobson, J. S., & De Vivo, I. (1993). Epidemiology of colorectal adenomatous polyps. Cancer Epidemiology, Biomarkers & Prevention, 2, 159–176.Google Scholar
  29. 29.
    Terry, P., Ekbom, A., Lichtenstein, P., Feychting, M., & Wolk, A. (2001). Long-term tobacco smoking and colorectal cancer in a prospective cohort study. International Journal of Cancer, 91, 585–587.CrossRefGoogle Scholar
  30. 30.
    Braganhol, E., Zamin, L. L., Canedo, A. D., Horn, F., Tamajusuku, A. S., Wink, M. R., et al. (2006). Antiproliferative effect of quercetin in the human U138MG glioma cell line. Anti-Cancer Drugs, 17, 663–671. doi:10.1097/01.cad.0000215063.23932.02.CrossRefGoogle Scholar
  31. 31.
    Conklin, C. M., Bechberger, J. F., MacFabe, D., Guthrie, N., Kurowska, E. M., & Naus, C. C. (2007). Genistein and quercetin increase connexin43 and suppress growth of breast cancer cells. Carcinogenesis, 28, 93–100. doi:10.1093/carcin/bgl106.CrossRefGoogle Scholar
  32. 32.
    Volate, S. R., Davenport, D. M., Muga, S. J., & Wargovich, M. J. (2005). Modulation of aberrant crypt foci and apoptosis by dietary herbal supplements (quercetin, curcumin, silymarin, ginseng and rutin). Carcinogenesis, 26, 1450–1456. doi:10.1093/carcin/bgi089.CrossRefGoogle Scholar
  33. 33.
    Dihal, A. A., de Boer, V. C., van der Woude, H., Tilburgs, C., Bruijntjes, J. P., Alink, G. M., et al. (2006). Quercetin, but not its glycosidated conjugate rutin, inhibits azoxymethane-induced colorectal carcinogenesis in F344 rats. Journal of Nutrition, 136, 2862–2867.Google Scholar
  34. 34.
    Fini, L., Piazzi, G., Daoud, Y., Selgrad, M., Maegawa, S., Garcia, M., et al. (2011). Chemoprevention of intestinal polyps in ApcMin/+ mice fed with western or balanced diets by drinking annurca apple polyphenol extract. Cancer Prevention Research (Philadelphia, Pa), 4, 907–915. doi:10.1158/1940-6207.CAPR-10-0359.CrossRefGoogle Scholar
  35. 35.
    National Cancer Institute. Prostate cancer. Retrieved July 27, 2012, from
  36. 36.
    Stearns, M. E., Amatangelo, M. D., Varma, D., Sell, C., & Goodyear, S. M. (2010). Combination therapy with epigallocatechin-3-gallate and doxorubicin in human prostate tumor modeling studies: Inhibition of metastatic tumor growth in severe combined immunodeficiency mice. American Journal of Pathology, 177, 3169–3179. doi:10.2353/ajpath.2010.100330.CrossRefGoogle Scholar
  37. 37.
    Kwon, G. T., Jung, J. I., Song, H. R., Woo, E. Y., Jun, J.-G., Kim, J.-K., et al. (2012). Piceatannol inhibits migration and invasion of prostate cancer cells: Possible mediation by decreased interleukin-6 signaling. Journal of Nutritional Biochemistry, 23, 228–238.CrossRefGoogle Scholar
  38. 38.
    Piotrowska, H., Kucinska, M., & Murias, M. (2012). Biological activity of piceatannol: Leaving the shadow of resveratrol. Mutation Research, 750, 60–82. doi:10.1016/j.mrrev.2011.11.001.CrossRefGoogle Scholar
  39. 39.
    Selander, K. S., Li, L., Watson, L., Merrell, M., Dahmen, H., Heinrich, P. C., et al. (2004). Inhibition of gp130 signaling in breast cancer blocks constitutive activation of Stat3 and inhibits in vivo malignancy. Cancer Research, 64, 6924–6933. doi:10.1158/0008-5472.CAN-03-2516.CrossRefGoogle Scholar
  40. 40.
    Buettner, R., Mora, L. B., & Jove, R. (2002). Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clinical Cancer Research, 8, 945–954.Google Scholar
  41. 41.
    Thakur, V. S., Gupta, K., & Gupta, S. (2012). Green tea polyphenols causes cell cycle arrest and apoptosis in prostate cancer cells by suppressing class I histone deacetylases. Carcinogenesis, 33, 377–384. doi:10.1093/carcin/bgr277.CrossRefGoogle Scholar
  42. 42.
    Siddiqui, I. A., Shukla, Y., Adhami, V. M., Sarfaraz, S., Asim, M., Hafeez, B. B., et al. (2008). Suppression of NFkappaB and its regulated gene products by oral administration of green tea polyphenols in an autochthonous mouse prostate cancer model. Pharmaceutical Research, 25, 2135–2142. doi:10.1007/s11095-008-9553-z.CrossRefGoogle Scholar
  43. 43.
    National Cancer Institute. Lung cancer. Retrieved July 27, 2012, from
  44. 44.
    Milligan, S. A., Burke, P., Coleman, D. T., Bigelow, R. L., Steffan, J. J., Carroll, J. L., et al. (2009). The green tea polyphenol EGCG potentiates the antiproliferative activity of c-Met and epidermal growth factor receptor inhibitors in non-small cell lung cancer cells. Clinical Cancer Research, 15, 4885–4894. doi:10.1158/1078-0432.CCR-09-0109.CrossRefGoogle Scholar
  45. 45.
    Lee, S. J., Chung, I. M., Kim, M. Y., Park, K. D., Park, W. H., & Moon, H. I. (2009). Inhibition of lung metastasis in mice by oligonol. Phytotherapy Research: PTR, 23, 1043–1046. doi:10.1002/ptr.2810.CrossRefGoogle Scholar
  46. 46.
    National Cancer Institute. What you need to know about breast cancer. Retrieved August 30, 2012, from
  47. 47.
    Luo, T., Wang, J., Yin, Y., Hua, H., Jing, J., Sun, X., et al. (2010). (−)-Epigallocatechin gallate sensitizes breast cancer cells to paclitaxel in a murine model of breast carcinoma. Breast Cancer Research, 12, R8. doi:10.1186/bcr2473.CrossRefGoogle Scholar
  48. 48.
    Sharma, R. A., McLelland, H. R., Hill, K. A., Ireson, C. R., Euden, S. A., Manson, M. M., et al. (2001). Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clinical Cancer Research, 7, 1894–1900.Google Scholar
  49. 49.
    Brown, V. A., Patel, K. R., Viskaduraki, M., Crowell, J. A., Perloff, M., Booth, T. D., et al. (2010). Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: Safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Research, 70, 9003–9011. doi:10.1158/0008-5472.CAN-10-2364.CrossRefGoogle Scholar
  50. 50.
    Patel, K. R., Brown, V. A., Jones, D. J., Britton, R. G., Hemingway, D., Miller, A. S., et al. (2010). Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients. Cancer Research, 70, 7392–7399. doi:10.1158/0008-5472.CAN-10-2027.CrossRefGoogle Scholar
  51. 51.
    McLarty, J., Bigelow, R. L., Smith, M., Elmajian, D., Ankem, M., & Cardelli, J. A. (2009). Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. Cancer Prevention Research (Philadelphia, Pa), 2, 673–682. doi:10.1158/1940-6207.CAPR-08-0167.CrossRefGoogle Scholar
  52. 52.
    Pantuck, A. J., Leppert, J. T., Zomorodian, N., Aronson, W., Hong, J., Barnard, R. J., et al. (2006). Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clinical Cancer Research, 12, 4018–4026. doi:10.1158/1078-0432.CCR-05-2290.CrossRefGoogle Scholar
  53. 53.
    Nguyen, M. M., Ahmann, F. R., Nagle, R. B., Hsu, C. H., Tangrea, J. A., Parnes, H. L., et al. (2012). Randomized, double-blind, placebo-controlled trial of polyphenon E in prostate cancer patients before prostatectomy: Evaluation of potential chemopreventive activities. Cancer Prevention Research (Philadelphia, Pa), 5, 290–298. doi:10.1158/1940-6207.CAPR-11-0306.CrossRefGoogle Scholar
  54. 54.
    Chow, H. H., Cai, Y., Hakim, I. A., Crowell, J. A., Shahi, F., Brooks, C. A., et al. (2003). Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clinical Cancer Research, 9, 3312–3319.Google Scholar
  55. 55.
    Neves, A. R., Lucio, M., Lima, J. L., & Reis, S. (2012). Resveratrol in medicinal chemistry: A critical review of its pharmacokinetics, drug-delivery, and membrane interactions. Current Medicinal Chemistry, 19, 1663–1681. doi:CMC-EPUB-20120117-009.CrossRefGoogle Scholar
  56. 56.
    Freitas, R. A., Jr. (2006). Pharmacytes: An ideal vehicle for targeted drug delivery. Journal of Nanoscience and Nanotechnology, 6, 2769–2775.CrossRefGoogle Scholar
  57. 57.
    Ferrari, M. (2005). Cancer nanotechnology: Opportunities and challenges. Nature Reviews Cancer, 5, 161–171. doi:10.1038/nrc1566.CrossRefGoogle Scholar
  58. 58.
    Singh, M., Bhatnagar, P., Srivastava, A. K., Kumar, P., Shukla, Y., & Gupta, K. C. (2011). Enhancement of cancer chemosensitization potential of cisplatin by tea polyphenols poly(lactide-co-glycolide) nanoparticles. Journal of Biomedical Nanotechnology, 7, 202.CrossRefGoogle Scholar
  59. 59.
    Yoshino, K., Suzuki, M., Sasaki, K., Miyase, T., & Sano, M. (1999). Formation of antioxidants from (−)-epigallocatechin gallate in mild alkaline fluids, such as authentic intestinal juice and mouse plasma. Journal of Nutritional Biochemistry, 10, 223–229.CrossRefGoogle Scholar
  60. 60.
    Kim, T. H., Jiang, H. H., Youn, Y. S., Park, C. W., Tak, K. K., Lee, S., et al. (2011). Preparation and characterization of water-soluble albumin-bound curcumin nanoparticles with improved antitumor activity. International Journal of Pharmaceutics, 403, 285–291. doi:10.1016/j.ijpharm.2010.10.041.CrossRefGoogle Scholar
  61. 61.
    John, T. A., Vogel, S. M., Tiruppathi, C., Malik, A. B., & Minshall, R. D. (2003). Quantitative analysis of albumin uptake and transport in the rat microvessel endothelial monolayer. American Journal of Physiology. Lung Cellular and Molecular Physiology, 284, L187–L196. doi:10.1152/ajplung.00152.2002.Google Scholar
  62. 62.
    Siddiqui, I. A., Adhami, V. M., Ahmad, N., & Mukhtar, H. (2010). Nanochemoprevention: Sustained release of bioactive food components for cancer prevention. Nutrition and Cancer, 62, 883–890. doi:10.1080/01635581.2010.509537.CrossRefGoogle Scholar
  63. 63.
    Akhtar, F., Rizvi, M. M., & Kar, S. K. (2011). Oral delivery of curcumin bound to chitosan nanoparticles cured Plasmodium yoelii infected mice. Biotechnology Advances,. doi:10.1016/j.biotechadv.2011.05.009.Google Scholar
  64. 64.
    Lu, J. J., Cai, Y. J., & Ding, J. (2011). Curcumin induces DNA damage and caffeine-insensitive cell cycle arrest in colorectal carcinoma HCT116 cells. Molecular and Cellular Biochemistry, 354, 247–252. doi:10.1007/s11010-011-0824-3.CrossRefGoogle Scholar
  65. 65.
    Choi, K. C., Park, S., Lim, B. J., Seong, A. R., Lee, Y. H., Shiota, M., et al. (2011). Procyanidin B3, an inhibitor of histone acetyltransferase, enhances the action of antagonist for prostate cancer cells via inhibition of p300-dependent acetylation of androgen receptor. Biochemical Journal, 433, 235–244. doi:10.1042/BJ20100980.CrossRefGoogle Scholar
  66. 66.
    Shim, J. H., Su, Z. Y., Chae, J. I., Kim, D. J., Zhu, F., Ma, W. Y., et al. (2010). Epigallocatechin gallate suppresses lung cancer cell growth through Ras-GTPase-activating protein SH3 domain-binding protein 1. Cancer Prevention Research (Philadelphia, Pa), 3, 670–679. doi:10.1158/1940-6207.CAPR-09-0185.CrossRefGoogle Scholar
  67. 67.
    Wen, W., Lu, J., Zhang, K., & Chen, S. (2008). Grape seed extract inhibits angiogenesis via suppression of the vascular endothelial growth factor receptor signaling pathway. Cancer Prevention Research (Philadelphia, Pa), 1, 554–561. doi:10.1158/1940-6207.CAPR-08-0040.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.The Pharmaceutical Research InstituteAlbany College of Pharmacy and Health SciencesRensselaerUSA

Personalised recommendations