ABSTRACT
Chemoprevention through the use of bioactive food components is a practical approach for cancer control. Despite abundant efficacy data under preclinical settings, this strategy has resulted in limited success for human cancer control. Amongst many reasons, inefficient systemic delivery and bioavailability of promising chemopreventive agents are considered to significantly contribute to such a disconnect. We recently introduced a novel concept in which we utilized nanotechnology for enhancing the outcome of chemoprevention (Cancer Res. 2009; 69:1712–6) and termed it nanochemoprevention. To establish the proof-of-principle of nanotechnology for cancer management, we determined the efficacy of a well-known chemopreventive agent epigallocatechin-3-gallate (EGCG) encapsulated in polylactic acid (PLA)-polyethylene glycol (PEG) nanoparticles in preclinical settings and observed that, compared to non-encapsulated EGCG, nano-EGCG retained its biological efficacy with over 10-fold dose advantage both in cell culture system and in vivo settings in athymic nude mice implanted with human prostate cancer cells. This study laid the foundation of nanochemoprevention by bioactive food components. Since oral consumption is the most desirable and acceptable form of delivery of bioactive food components, it will be important to develop nanoparticles containing bioactive food components that are suitable for oral consumption for which experiments are underway in this laboratory.
Similar content being viewed by others
REFERENCES
Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 2003;3:768–80.
Siddiqui IA, Afaq F, Adhami VM, Mukhtar H. Prevention of prostate cancer through custom tailoring of chemopreventive regimen. Chem Biol Interact. 2008;171:122–32.
Khan N, Afaq F, Mukhtar H. Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxid Redox Signal. 2008;10:475–510.
Syed DN, Khan N, Afaq F, Mukhtar H. Chemoprevention of prostate cancer through dietary agents: progress and promise. Cancer Epidemiol Biomarkers Prev. 2007;16:2193–203.
Milner JA. Diet and cancer: facts and controversies. Nutr Cancer. 2006;56:216–24.
Greenwald P. Clinical trials in cancer prevention: current results and perspectives for the future. J Nutr. 2004;134:3507S–12.
Birt DF, Hendrich S, Wang W. Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacol Ther. 2001;90:157–77.
Amin AR, Kucuk O, Khuri FR, Shin DM. Perspectives for cancer prevention with natural compounds. J Clin Oncol. 2009;27:2712–25.
Bode AM, Dong Z. Cancer prevention research—then and now. Nat Rev Cancer. 2009;9:508–16.
Khan N, Adhami VM, Mukhtar H. Apoptosis by dietary agents for prevention and treatment of cancer. Biochem Pharmacol. 2008;76:1333–9.
Nishiyama N. Nanomedicine: nanocarriers shape up for long life. Nat Nanotechnol. 2007;2:203–4.
Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer. 2005;5:161–71.
Nie S, Xing Y, Kim GJ, Simons JW. Nanotechnology applications in cancer. Annu Rev Biomed Eng. 2007;9:257–88.
Cuenca AG, Jiang H, Hochwald SN, Delano M, Cance WG, Grobmyer SR. Emerging implications of nanotechnology on cancer diagnostics and therapeutics. Cancer. 2006;107:459–66.
Wang X, Yang L, Chen ZG, Shin DM. Application of nanotechnology in cancer therapy and imaging. CA Cancer J Clin. 2008;58:97–110.
Niemeyer CM. Semi-synthetic nucleic acid-protein conjugates: applications in life sciences and nanobiotechnology. J Biotechnol. 2001;82:47–66.
Siddiqui IA, Adhami VM, Bharali DJ, Hafeez BB, Asim M, Khwaja SI, et al. Introducing nanochemoprevention as a novel approach for cancer control: proof of principle with green tea polyphenol epigallocatechin-3-gallate. Cancer Res. 2009;69:1712–6.
Kaul G, Amiji M. Biodistribution and targeting potential of poly(ethylene glycol)-modified gelatin nanoparticles in subcutaneous murine tumor model. J Drug Target. 2004;12:585–91.
Kaul G, Amiji M. Tumor-targeted gene delivery using poly(ethylene glycol)-modified gelatin nanoparticles: in vitro and in vivo studies. Pharm Res. 2005;22:951–61.
Cherian AK, Rana AC, Jain SK. Self-assembled carbohydrate-stabilized ceramic nanoparticles for the parenteral delivery of insulin. Drug Dev Ind Pharm. 2000;26:459–63.
Sahoo SK, Labhasetwar V. Nanotech approaches to drug delivery and imaging. Drug Discov Today. 2003;8:1112–20.
Torchilin VP. Targeted polymeric micelles for delivery of poorly soluble drugs. Cell Mol Life Sci. 2004;61:2549–59.
Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V, Langer R. Biodegradable long-circulating polymeric nanospheres. Science. 1994;263:1600–3.
Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007;2:751–60.
Kawasaki ES, Player A. Nanotechnology, nanomedicine, and the development of new, effective therapies for cancer. Nanomedicine. 2005;1:101–9.
Gref R, Domb A, Quellec P, Blunk T, Müller RH, Verbavatz JM, et al. The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres. Adv Drug Deliv Rev. 1995;16:215–33.
Deng C, Tian H, Zhang P, Sun J, Chen X, Jing X. Synthesis and characterization of RGD peptide grafted poly(ethylene glycol)-b-poly(L-lactide)-b-poly(L-glutamic acid) triblock copolymer. Biomacromolecules. 2006;7:590–6.
Mosqueira VC, Legrand P, Morgat JL, Vert M, Mysiakine E, Gref R, et al. Biodistribution of long-circulating PEG-grafted nanocapsules in mice: effects of PEG chain length and density. Pharm Res. 2001;18:1411–9.
Stolnik S, Dunn SE, Garnett MC, Davies MC, Coombes AG, Taylor DC, et al. Surface modification of poly(lactide-co-glycolide) nanospheres by biodegradable poly(lactide)-poly(ethylene glycol) copolymers. Pharm Res. 1994;11:1800–8.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.
Khan N, Afaq F, Saleem M, Ahmad N, Mukhtar H. Targeting multiple signaling pathways by green tea polyphenol (−)-epigallocatechin-3-gallate. Cancer Res. 2006;66:2500–5.
Stuart EC, Scandlyn MJ, Rosengren RJ. Role of epigallocatechin gallate (EGCG) in the treatment of breast and prostate cancer. Life Sci. 2006;79:2329–36.
Saleem M, Adhami VM, Siddiqui IA, Mukhtar H. Tea beverage in chemoprevention of prostate cancer: a mini-review. Nutr Cancer. 2003;47:13–23.
McLarty J, Bigelow RL, Smith M, Elmajian D, Ankem M, Cardelli JA. 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 Prev Res (Phila PA). 2009;2:673–82.
Butt MS, Sultan MT. Green tea: nature’s defense against malignancies. Crit Rev Food Sci Nutr. 2009;49:463–73.
Khan N, Mukhtar H. Multitargeted therapy of cancer by green tea polyphenols. Cancer Lett. 2008;269:269–80.
Mukhtar H, Ahmad N. Green tea in chemoprevention of cancer. Toxicol Sci. 1999;52:111–7.
Ahmad N, Feyes DK, Nieminen AL, Agarwal R, Mukhtar H. Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. J Natl Cancer Inst. 1997;89:1881–6.
Henning SM, Niu Y, Lee NH, Thames GD, Minutti RR, Wang H, et al. Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea, or a green tea extract supplement. Am J Clin Nutr. 2004;80:1558–64.
Lee MJ, Maliakal P, Chen L, Meng X, Bondoc FY, Prabhu S, et al. Pharmacokinetics of tea catechins after ingestion of green tea and (−)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability. Cancer Epidemiol Biomarkers Prev. 2002;11:1025–32.
Lambert JD, Lee MJ, Lu H, Meng X, Hong JJ, Seril DN, et al. Epigallocatechin-3-gallate is absorbed but extensively glucuronidated following oral administration to mice. J Nutr. 2003;133:4172–7.
Lambert JD, Hong J, Kim DH, Mishin VM, Yang CS. Piperine enhances the bioavailability of the tea polyphenol (−)-epigallocatechin-3-gallate in mice. J Nutr. 2004;134:1948–52.
Cao Y, Cao R. Angiogenesis inhibited by drinking tea. Nature. 1999;398:381.
Mantena SK, Roy AM, Katiyar SK. Epigallocatechin-3-gallate inhibits photocarcinogenesis through inhibition of angiogenic factors and activation of CD8+ T cells in tumors. Photochem Photobiol. 2005;81:1174–9.
Shankar S, Ganapathy S, Hingorani SR, Srivastava RK. EGCG inhibits growth, invasion, angiogenesis and metastasis of pancreatic cancer. Front Biosci. 2008;13:440–52.
Tang FY, Chiang EP, Shih CJ. Green tea catechin inhibits ephrin-A1-mediated cell migration and angiogenesis of human umbilical vein endothelial cells. J Nutr Biochem. 2007;18:391–9.
Siddiqui IA, Malik A, Adhami VM, Asim M, Hafeez BB, Sarfaraz S, et al. Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis. Oncogene. 2008;27:2055–63.
Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281:1591–7.
Adhami VM, Malik A, Zaman N, Sarfaraz S, Siddiqui IA, Syed DN, et al. Combined inhibitory effects of green tea polyphenols and selective cyclooxygenase-2 inhibitors on the growth of human prostate cancer cells both in vitro and in vivo. Clin Cancer Res. 2007;13:1611–9.
Zhang L, Gu FX, Chan JM, Wang AZ, Langer RS, Farokhzad OC. Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol Ther. 2008;83:761–9.
Han DW, Lee JJ, Jung DY, Park JC, Hyon SH. Development of epigallocatechin gallate-eluting polymeric stent and its physicochemical, biomechanical and biological evaluations. Biomed Mater. 2009;4:44104.
Italia JL, Datta P, Ankola DD, Kumar MNVR. Nanoparticles enhance per oral bioavailability of poorly available molecules: epigallocatechin gallate nanoparticles ameliorates cyclosporine induced nephrotoxicity in rats at three times lower dose than oral solution. Journal of Biomedical Nanotechnology. 2008;4:304–12.
Sahu A, Bora U, Kasoju N, Goswami P. Synthesis of novel biodegradable and self-assembling methoxy poly(ethylene glycol)-palmitate nanocarrier for curcumin delivery to cancer cells. Acta Biomater. 2008;4:1752–61.
Thangapazham RL, Puri A, Tele S, Blumenthal R, Maheshwari RK. Evaluation of a nanotechnology-based carrier for delivery of curcumin in prostate cancer cells. Int J Oncol. 2008;32:1119–23.
Das RK, Kasoju N, Bora U. Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomedicine. 2009.
Merrell JG, McLaughlin SW, Tie L, Laurencin CT, Chen AF, Nair LS. Curcumin loaded poly(epsilon-caprolactone) nanofibers: diabetic wound dressing with antioxidant and anti-inflammatory properties. Clin Exp Pharmacol Physiol. 2009;36(12):1149–56.
Li J, Wang Y, Yang C, Wang P, Oelschlager DK, Zheng Y, et al. Polyethylene glycosylated curcumin conjugate inhibits pancreatic cancer cell growth through inactivation of Jab1. Mol Pharmacol. 2009;76:81–90.
Shao J, Li X, Lu X, Jiang C, Hu Y, Li Q, et al. Enhanced growth inhibition effect of resveratrol incorporated into biodegradable nanoparticles against glioma cells is mediated by the induction of intracellular reactive oxygen species levels. Colloids Surf B Biointerfaces. 2009;72:40–7.
Lu X, Ji C, Xu H, Li X, Ding H, Ye M, et al. Resveratrol-loaded polymeric micelles protect cells from Abeta-induced oxidative stress. Int J Pharm. 2009;375:89–96.
Narayanan NK, Nargi D, Randolph C, Narayanan BA. Liposome encapsulation of curcumin and resveratrol in combination reduces prostate cancer incidence in PTEN knockout mice. Int J Cancer. 2009;125:1–8.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Siddiqui, I.A., Mukhtar, H. Nanochemoprevention by Bioactive Food Components: A Perspective. Pharm Res 27, 1054–1060 (2010). https://doi.org/10.1007/s11095-010-0087-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11095-010-0087-9