Application of bioactive quercetin in oncotherapy: From nutrition to nanomedicine

Molecules

Volumn 21, Issue 1, 2016, Pages

  Nam, Ju Suk ^a   Sharma, Ashish Ranjan ^a   Nguyen, Lich Thi ^a   Chakraborty, Chiranjib ^b   Sharma, Garima ^a,c   Lee, Sang Soo ^a  

^a Hallym University   (South Korea)

^b GALGOTIAS UNIVERSITY   (India)

^c AMITY UNIVERSITY   (India)

Author keywords

Anticancer; Bioavailability; Nanoformulation; Oncotherapy; Phytochemical; Quercetin

Indexed keywords

ANTINEOPLASTIC AGENT; ANTIOXIDANT; DRUG CARRIER; NANOPARTICLE; QUERCETIN;

ANALOGS AND DERIVATIVES; ANIMAL; BIOAVAILABILITY; CELL PROLIFERATION; CHEMISTRY; DIETARY SUPPLEMENT; DRUG DELIVERY SYSTEM; DRUG EFFECTS; HUMAN; MEDICINAL CHEMISTRY; METABOLISM; NANOMEDICINE; NEOPLASMS; SIGNAL TRANSDUCTION;

ANIMALS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; ANTIOXIDANTS; BIOLOGICAL AVAILABILITY; CELL PROLIFERATION; CHEMISTRY, PHARMACEUTICAL; DIETARY SUPPLEMENTS; DRUG CARRIERS; DRUG DELIVERY SYSTEMS; HUMANS; NANOMEDICINE; NANOPARTICLES; NEOPLASMS; QUERCETIN; SIGNAL TRANSDUCTION;

EID: 85000763639     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules21010108     Document Type: Review

References (162)

1. Xiao, Z.P.; Peng, Z.Y.; Peng, M.J.; Yan, W.B.; Ouyang, Y.Z.; Zhu, H.L. Flavonoids health benefits and their molecular mechanism. Mini-Rev. Med. Chem. 2011, 11, 169-177. [Cross Ref] [Pub Med].
2. Haddad, A.Q.; Fleshner, N.; Nelson, C.; Saour, B.; Musquera, M.; Venkateswaran, V.; Klotz, L. Anti proliferative mechanisms of the flavonoids 2, 21-dihydroxychalcone and fisetin in human prostate cancer cells. Nutr. Cancer 2010, 62, 668-681. [Cross Ref] [Pub Med].
3. Formica, J.V.; Regelson, W. Review of the biology of Quercetin and related bio flavonoids. Food Chem. Toxicol. 1995, 33, 1061-1080. [Cross Ref].
4. Kumar, S.; Pandey, A.K. Chemistry and biological activities of flavonoids: An overview. Sci. World J. 2013, 2013. [Cross Ref] [Pub Med].
5. Moon, J.H.; Tsushida, T.; Nakahara, K.; Terao, J. Identification of quercetin 3-O-D-glucuronide as an antioxidative metabolite in rat plasma after oral administration of quercetin. Free Radic. Biol. Med. 2001, 30, 1274-1285. [Cross Ref].
6. Bors, W.; Michel, C.; Saran, M. Flavonoid antioxidants: Rate constants for reactions with oxygen radicals. Methods Enzymol. 1994, 234, 420-429. [Pub Med].
7. Prior, R.L. Fruits and vegetables in the prevention of cellular oxidative damage. Am. J. Clin. Nutr. 2003, 78, 570S-578S. [Pub Med].
8. Erkoç, S.; Erkoç, F.; Keskin, N. Theoretical investigation of quercetin and its radical isomers. J. Mol. Struct. The Ochem 2003, 631, 141-146. [Cross Ref].
9. Kampa, M.; Hatzoglou, A.; Notas, G.; Damianaki, A.; Bakogeorgou, E.; Gemetzi, C.; Kouroumalis, E.; Martin, P.-M.; Castanas, E. Wine antioxidant polyphenols inhibit the proliferation of human prostate cancer cell lines. Nutr. Cancer 2000, 37, 223-233. [Cross Ref] [Pub Med].
10. American Cancer Society. Cancer Facts and Figures 2015; American Cancer Society: Atlanta, GA, USA, 2015.
11. Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2015. CA Cancer J. Clin. 2015, 65, 5-29. [Cross Ref] [Pub Med].
12. Donaldson, M.S. Nutrition and cancer: A review of the evidence for an anti-cancer diet. Nutr. J. 2004, 3. [Cross Ref] [Pub Med].
13. Riboli, E.; Norat, T. Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am. J. Clin. Nutr. 2003, 78, 559S-569S. [Pub Med].
14. Nabavi, S.F.; Daglia, M.; Moghaddam, A.H.; Habtemariam, S.; Nabavi, S.M. Curcumin and liver disease: from chemistry to medicine. Compr. Rev. Food Sci. Food Saf. 2014, 13, 62-77. [Cross Ref].
15. Lee, K.W.; Bode, A.M.; Dong, Z. Molecular targets of phytochemicals for cancer prevention. Nat. Rev. Cancer 2011, 11, 211-218. [Cross Ref] [Pub Med].
16. Goodman, M.; Bostick, R.M.; Kucuk, O.; Jones, D.P. Clinical trials of antioxidants as cancer prevention agents: Past, present, and future. Free Radic. Biol. Med. 2011, 51, 1068-1084. [Cross Ref] [Pub Med].
17. Shu, L.; Cheung, K.L.; Khor, T.O.; Chen, C.; Kong, A.N. Phyto chemicals: Cancer chemoprevention and suppression of tumor onset and metastasis. Cancer Metastasis Rev. 2010, 29, 483-502. [Cross Ref] [Pub Med].
18. Bishayee, A. Cancer prevention and treatment with resveratrol: From rodent studies to clinical trials. Cancer Prev. Res. 2009, 2, 409-418. [Cross Ref] [Pub Med].
19. Yuan, Z.; Long, C.; Junming, T.; Qihuan, L.; Youshun, Z.; Chan, Z. Quercetin-induced apoptosis of HL-60 cells by reducing PI3K/Akt. Mol. Biol. Rep. 2012, 39, 7785-7793. [Cross Ref] [Pub Med].
20. Shan, B.E.;Wang, M.X.; Li, R.Q. Quercetin inhibit human SW480 colon cancer growth in association with inhibition of cyclin D1 and survivin expression through Wnt/β-catenin signaling pathway. Cancer Investig. 2009, 27, 604-612. [Cross Ref] [Pub Med].
21. Kim, H.; Seo, E.M.; Sharma, A.R.; Ganbold, B.; Park, J.; Sharma, G.; Kang, Y.H.; Song, D.K.; Lee, S.S.; Nam, J.S. Regulation of Wnt signaling activity for growth suppression induced by quercetin in 4T1 murine mammary cancer cells. Int. J. Oncol. 2013, 43, 1319-1325. [Pub Med].
22. Huang, Y.T.; Hwang, J.J.; Lee, P.P.; Ke, F.C.; Huang, J.H.; Huang, C.J.; Kandaswami, C.; Middleton, E.; Lee, M.T. Effects of luteolin and quercetin, inhibitors of tyrosine kinase, on cell growth and metastasis-associated properties in A431 cells overexpressing epidermal growth factor receptor. Br. J. Pharmacol. 1999, 128, 999-1010. [Cross Ref] [Pub Med].
23. Cai, X.; Fang, Z.; Dou, J.; Yu, A.; Zhai, G. Bioavailability of quercetin: Problems and promises. Curr. Med. Chem. 2013, 20, 2572-2582. [Cross Ref] [Pub Med].
24. Khushnud, T.; Mousa, S.A. Potential role of naturally derived polyphenols and their nanotechnology delivery in cancer. Mol. Biotechnol. 2013, 55, 78-86. [Cross Ref] [Pub Med].
25. Wang, S.; Zhang, J.; Chen, M.; Wang, Y. Delivering flavonoids into solid tumors using nanotechnologies. Expert Opin. Drug Deliv. 2013, 10, 1411-1428. [Cross Ref] [Pub Med].
26. Ferry, D.R.; Smith, A.; Malkhandi, J.; Fyfe, D.W.; deTakats, P.G.; Anderson, D.; Baker, J.; Kerr, D.J. Phase I clinical trial of the flavonoid quercetin: Pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin. Cancer. Res. 1996, 2, 659-668. [Pub Med].
27. Mukerjee, A.; Vishwanatha, J.K. Formulation, characterization and evaluation of curcumin-loaded PLGA nanospheres for cancer therapy. Anticancer Res. 2009, 29, 3867-3875. [Pub Med].
28. Jeetah, R.; Bhaw-Luximon, A.; Jhurry, D. Nanopharmaceutics: Phytochemical-based controlled or sustained drug-delivery systems for cancer treatment. J. Biomed. Nanotechnol. 2014, 10, 1810-1840. [Cross Ref] [Pub Med].
29. Sharma, A.R.; Kundu, S.K.; Nam, J.S.; Sharma, G.; Priya Doss, C.G.; Lee, S.S.; Chakraborty, C. Next generation delivery system for proteins and genes of therapeutic purpose: Why and how Biomed. Res. Int. 2014, 2014, 327950. [Cross Ref] [Pub Med].
30. Sharma, G.; Sharma, A.R.; Nam, J.S.; Doss, G.P.; Lee, S.S.; Chakraborty, C. Nanoparticle based insulin delivery system: The next generation efficient therapy for Type 1 diabetes. J. Nanobiotechnol. 2015, 13, 74. [Cross Ref] [Pub Med].
31. Mulik, R.S.; Monkkonen, J.; Juvonen, R.O.; Mahadik, K.R.; Paradkar, A.R. Apoptosis-induced anticancer effect of transferrin-conjugated solid lipid nanoparticles of curcumin. Cancer Nanotechnol. 2012, 3, 65-81. [Cross Ref] [Pub Med].
32. Morand, C.; Crespy, V.; Manach, C.; Besson, C.; Demigne, C.; Remesy, C. Plasma metabolites of quercetin and their antioxidant properties. Am. J. Physiol. 1998, 275, R212-R219. [Pub Med].
33. Cornard, J.P.; Dangleterre, L.; Lapouge, C. Computational and spectroscopic characterization of the molecular and electronic structure of the Pb(II)-quercetin complex. J. Phys. Chem. A 2005, 109, 10044-10051. [Cross Ref] [Pub Med].
34. Mendoza-Wilson, A.M.A.; Glossman-Mitnik, D. CHIH-DFT determination of the molecular structure, infrared and ultraviolet spectra of the flavonoid quercetin. J. Mol. Str. THEOCHEM 2004, 681, 71-76. [Cross Ref].
35. Fischer, C.; Speth, V.; Fleig-Eberenz, S.; Neuhaus, G. Induction of zygotic poly embryos in wheat: Influence of auxin polar transport. Plant Cell 1997, 9, 1767-1780. [Cross Ref] [Pub Med].
36. Williams, C.A.; Grayer, R.J. Anthocyanins and other flavonoids. Nat. Prod. Rep. 2004, 21, 539-573. [Cross Ref] [Pub Med].
37. Harborne, J.B.;Williams, C.A. Advances in flavonoid research since 1992. Phytochemistry 2000, 55, 481-504. [Cross Ref].
38. Fang, N.; Yu, S.; Mabry, T.J. Flavonoids from Ageratina calophylla. Phytochemistry 1986, 25, 2684-2686. [Cross Ref].
39. Zeng, L.-M.;Wang, C.-J.; Su, J.-Y.; Li, D.; Owen, N.L.; Lu, Y.; Lu, N.; Zheng, Q.-T. Flavonoids from the red alga Acanthophora spicifera. Chin. J. Chem. 2001, 19, 1097-1100. [Cross Ref].
40. Dal Santo, S.; Tornielli, G.B.; Zenoni, S.; Fasoli, M.; Farina, L.; Anesi, A.; Guzzo, F.; Delledonne, M.; Pezzotti, M. The plasticity of the grapevine berry transcriptome. Genome Biol. 2013, 14. [Cross Ref] [Pub Med].
41. Rice-Evans, C.; Miller, N.; Paganga, G. Antioxidant properties of phenolic compounds. Trends Plant Sci. 1997, 2, 152-159. [Cross Ref].
42. Heijnen, C.G.; Haenen, G.R.; Oostveen, R.M.; Stalpers, E.M.; Bast, A. Protection of flavonoids against lipid peroxidation: The structure activity relationship revisited. Free Radic. Res. 2002, 36, 575-581. [Cross Ref] [Pub Med].
43. Liu, L.P.; Liao, Z.P.; Yin, D.; Li, W.D.; Liu, D.; Li, Q.; Huang, Q.R.; Yang, Y.F.; He, M. The protective effects of Polygonum multiflorum stilbene glycoside preconditioning in an ischemia/reperfusion model of HUVECs. Acta Pharmacol. Sin. 2010, 31, 405-412. [Cross Ref] [Pub Med].
44. Zhu, Q.Y.; Huang, Y.; Chen, Z.Y. Interaction between flavonoids and alpha-tocopherol in human low density lipoprotein. J. Nutr. Biochem. 2000, 11, 14-21. [Cross Ref].
45. Borghetti, G.S.; Carini, J.P.; Honorato, S.B.; Ayala, A.P.; Moreira, J.C. F.; Bassani, V.L. Physicochemical properties and thermal stability of quercetin hydrates in the solid state. Thermochim. Acta 2012, 539, 109-114. [Cross Ref].
46. Ghosh, D.; Ghosh, S.; Sarkar, S.; Ghosh, A.; Das, N.; Das Saha, K.; Mandal, A.K. Quercetin in vesicular delivery systems: Evaluation in combating arsenic-induced acute liver toxicity associated gene expression in rat model. Chem. Biol. Interact. 2010, 186, 61-71. [CrossRef] [PubMed].
47. Bischoff, S.C. Quercetin: Potentials in the prevention and therapy of disease. Curr. Opin. Clin. Nutr. Metab. Care 2008, 11, 733-740. [Cross Ref] [Pub Med].
48. Harnly, J.M.; Doherty, R.F.; Beecher, G.R.; Holden, J.M.; Haytowitz, D.B.; Bhagwat, S.; Gebhardt, S. Flavonoid content of U.S. fruits, vegetables, and nuts. J. Agric. Food Chem. 2006, 54, 9966-9977. [Cross Ref] [Pub Med].
49. Sampson, L.; Rimm, E.; Hollman, P.C.; de Vries, J.H.; Katan, M.B. Flavonol and flavone intakes in US health professionals. J. Am. Diet Assoc. 2002, 102, 1414-1420. [Cross Ref].
50. Brown, J.P. A review of the genetic effects of naturally occurring flavonoids, anthraquinones and related compounds. Mutat. Res. 1980, 75, 243-277. [Cross Ref].
51. Jones, E.; Hughes, R.E. Quercetin, flavonoids and the life-span of mice. Exp. Gerontol. 1982, 17, 213-217. [Cross Ref].
52. Johannot, L.; Somerset, S.M. Age-related variations in flavonoid intake and sources in the Australian population. Public Health Nutr. 2006, 9, 1045-1054. [Cross Ref] [Pub Med].
53. Nishimuro, H.; Ohnishi, H.; Sato, M.; Ohnishi-Kameyama, M.; Matsunaga, I.; Naito, S.; Ippoushi, K.; Oike, H.; Nagata, T.; Akasaka, H.; et al. Estimated daily intake and seasonal food sources of quercetin in Japan. Nutrients 2015, 7, 2345-2358. [Cross Ref] [Pub Med].
54. Jackson, M.J. The assessment of bioavailability of micronutrients: Introduction. Eur. J. Clin. Nutr. 1997, 51 (Suppl. 1), S1-S2. [Pub Med].
55. Tamura, G.; Gold, C.; Ferro-Luzzi, A.; Ames, B.N. Fecalase: A model for activation of dietary glycosides to mutagens by intestinal flora. Proc. Natl. Acad. Sci. USA 1980, 77, 4961-4965. [Cross Ref] [Pub Med].
56. Crespy, V.; Morand, C.; Besson, C.; Manach, C.; Demigne, C.; Remesy, C. Quercetin, but not its glycosides, is absorbed from the rat stomach. J. Agric. Food Chem. 2002, 50, 618-621. [Cross Ref] [Pub Med].
57. Crespy, V.; Morand, C.; Manach, C.; Besson, C.; Demigne, C.; Remesy, C. Part of quercetin absorbed in the small intestine is conjugated and further secreted in the intestinal lumen. Am. J. Physiol. 1999, 277, G120-G126. [Pub Med].
58. Nait Chabane, M.; al Ahmad, A.; Peluso, J.; Muller, C.D.; Ubeaud, G. Quercetin and naringenin transport across human intestinal Caco-2 cells. J. Pharm. Pharmacol. 2009, 61, 1473-1483. [Cross Ref] [Pub Med].
59. Moon, J.H.; Nakata, R.; Oshima, S.; Inakuma, T.; Terao, J. Accumulation of quercetin conjugates in blood plasma after the short-term ingestion of onion by women. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000, 279, R461-R467. [Pub Med].
60. Conquer, J.A.; Maiani, G.; Azzini, E.; Raguzzini, A.; Holub, B.J. Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects. J. Nutr. 1998, 128, 593-597. [Pub Med].
61. Walle, T.; Walle, U.K.; Halushka, P.V. Carbon Dioxide Is the Major Metabolite of Quercetin in Humans. J. Nutr. 2001, 131, 2648-2652. [Pub Med].
62. Justino, G.C.; Santos, M.R.; Canario, S.; Borges, C.; Florencio, M.H.; Mira, L. Plasma quercetin metabolites: Structure-antioxidant activity relationships. Arch. Biochem. Biophys. 2004, 432, 109-121. [Cross Ref] [Pub Med].
63. Mullen, W.; Rouanet, J.M.; Auger, C.; Teissedre, P.L.; Caldwell, S.T.; Hartley, R.C.; Lean, M.E.; Edwards, C.A.; Crozier, A. Bioavailability of [2-(14)C]quercetin-41-glucoside in rats. J. Agric. Food Chem. 2008, 56, 12127-12137. [Cross Ref] [Pub Med].
64. Hong, Y.J.; Mitchell, A.E. Metabolic profiling of flavonol metabolites in human urine by liquid chromatography and tandem mass spectrometry. J. Agric. Food Chem. 2004, 52, 6794-6801. [Cross Ref] [Pub Med].
65. Okamoto, T. Safety of quercetin for clinical application (Review). Int. J. Mol. Med. 2005, 16, 275-278. [Cross Ref] [Pub Med].
66. Crebelli, R.; Aquilina, G.; Falcone, E.; Carere, A. Urinary and faecal mutagenicity in Sprague-Dawley rats dosed with the food mutagens quercetin and rutin. Food Chem. Toxicol. 1987, 25, 9-15. [Cross Ref].
67. Harwood, M.; Danielewska-Nikiel, B.; Borzelleca, J.F.; Flamm, G.W.;Williams, G.M.; Lines, T.C. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem. Toxicol. 2007, 45, 2179-2205. [Cross Ref] [Pub Med].
68. Suolinna, E.M.; Buchsbaum, R.N.; Racker, E. The effect of flavonoids on aerobic glycolysis and growth of tumor cells. Cancer Res. 1975, 35, 1865-1872. [Pub Med].
69. Hosokawa, N.; Hirayoshi, K.; Nakai, A.; Hosokawa, Y.; Marui, N.; Yoshida, M.; Sakai, T.; Nishino, H.; Aoike, A.; Kawai, K.; et al. Flavonoids inhibit the expression of heat shock proteins. Cell Struct. Funct. 1990, 15, 393-401. [Cross Ref] [Pub Med].
70. Scambia, G.; Ranelletti, F.O.; Panici, P.B.; Piantelli, M.; Bonanno, G.; de Vincenzo, R.; Ferrandina, G.; Rumi, C.; Larocca, L.M.; Mancuso, S. Inhibitory effect of quercetin on OVCA 433 cells and presence of type II oestrogen binding sites in primary ovarian tumours and cultured cells. Br. J. Cancer 1990, 62, 942-946. [Cross Ref] [Pub Med].
71. p53 in hepatocellular carcinoma (HepG2) cell line. Mol. Biol. Rep. 2015, 42, 1419-1429. [Cross Ref] [Pub Med].
72. Yoshida, M.; Sakai, T.; Hosokawa, N.; Marui, N.; Matsumoto, K.; Fujioka, A.; Nishino, H.; Aoike, A. The effect of quercetin on cell cycle progression and growth of human gastric cancer cells. FEBS Lett. 1990, 260, 10-13. [Cross Ref].
73. Edwards, J.M.; Raffauf, R.F.; le Quesne, P.W. Antineoplastic activity and cytotoxicity of flavones, isoflavones, and flavanones. J. Nat. Prod. 1979, 42, 85-91. [Cross Ref] [Pub Med].
74. Angst, E.; Park, J.L.; Moro, A.; Lu, Q.Y.; Lu, X.; Li, G.; King, J.; Chen, M.; Reber, H.A.; Go, V.L.; et al. The flavonoid quercetin inhibits pancreatic cancer growth in vitro and in vivo. Pancreas 2013, 42, 223-229. [Cross Ref] [Pub Med].
75. Bruning, A. Inhibition of mTOR signaling by quercetin in cancer treatment and prevention. Anticancer Agents Med. Chem. 2013, 13, 1025-1031. [Cross Ref] [Pub Med].
76. Gulati, N.; Laudet, B.; Zohrabian, V.M.; Murali, R.; Jhanwar-Uniyal, M. The antiproliferative effect of Quercetin in cancer cells is mediated via inhibition of the PI3K-Akt/PKB pathway. Anticancer Res. 2006, 26, 1177-1181. [Pub Med].
77. Jeong, J.H.; An, J.Y.; Kwon, Y.T.; Li, L.Y.; Lee, Y.J. Quercetin-induced ubiquitination and down-regulation of Her-2/neu. J. Cell. Biochem. 2008, 105, 585-595. [Cross Ref] [Pub Med].
78. p53 and decrease in energy metabolism. Nutr. Cancer 2015, 67, 354-363. [Cross Ref] [Pub Med].
79. Firdous, A.B.; Sharmila, G.; Balakrishnan, S.; RajaSingh, P.; Suganya, S.; Srinivasan, N.; Arunakaran, J. Quercetin, a natural dietary flavonoid, acts as a chemopreventive agent against prostate cancer in an in vivo model by inhibiting the EGFR signaling pathway. Food Funct. 2014, 5, 2632-2645. [Cross Ref] [Pub Med].
80. p27 in human hepatoma cell line (HepG2). Methods Find Exp. Clin. Pharmacol. 2007, 29, 179-183. [Cross Ref] [Pub Med].
81. p53 induction and NF-kappaB inhibition. Eur. J. Pharmacol. 2010, 649, 84-91. [Cross Ref] [Pub Med].
82. Yeh, S.L.; Yeh, C.L.; Chan, S.T.; Chuang, C.H. Plasma rich in quercetin metabolites induces G2/M arrest by upregulating PPAR-gamma expression in human A549 lung cancer cells. Planta Med. 2011, 77, 992-998. [Cross Ref] [Pub Med].
83. Catanzaro, D.; Ragazzi, E.; Vianello, C.; Caparrotta, L.; Montopoli, M. Effect of Quercetin on Cell Cycle and Cyclin Expression in Ovarian Carcinoma and Osteosarcoma Cell Lines. Nat. Prod. Commun. 2015, 10, 1365-1368. [Pub Med].
84. Huang, C.Y.; Chan, C.Y.; Chou, I.T.; Lien, C.H.; Hung, H.C.; Lee, M.F. Quercetin induces growth arrest through activation of FOXO1 transcription factor in EGFR-overexpressing oral cancer cells. J. Nutr. Biochem. 2013, 24, 1596-1603. [Cross Ref] [Pub Med].
85. Liabakk, N.B.; Talbot, I.; Smith, R.A.; Wilkinson, K.; Balkwill, F. Matrix metalloprotease 2 (MMP-2) and matrix metalloprotease 9 (MMP-9) type IV collagenases in colorectal cancer. Cancer Res. 1996, 56, 190-196. [Pub Med].
86. Lin, C.W.; Hou, W.C.; Shen, S.C.; Juan, S.H.; Ko, C.H.; Wang, L.M.; Chen, Y.C. Quercetin inhibition of tumor invasion via suppressing PKC -/ERK/AP-1-dependent matrix metalloproteinase-9 activation in breast carcinoma cells. Carcinogenesis 2008, 29, 1807-1815. [Cross Ref] [Pub Med].
87. Hwang, M.K.; Song, N.R.; Kang, N.J.; Lee, K.W.; Lee, H.J. Activation of phosphatidylinositol 3-kinase is required for tumor necrosis factor-alpha-induced upregulation of matrix metalloproteinase-9: Its direct inhibition by quercetin. Int. J. Biochem. Cell Biol. 2009, 41, 1592-1600. [Cross Ref] [Pub Med].
88. Lee, L.T.; Huang, Y.T.; Hwang, J.J.; Lee, A.Y.; Ke, F.C.; Huang, C.J.; Kandaswami, C.; Lee, P.P.; Lee, M.T. Transinactivation of the epidermal growth factor receptor tyrosine kinase and focal adhesion kinase phosphorylation by dietary flavonoids: Effect on invasive potential of human carcinoma cells. Biochem. Pharmacol. 2004, 67, 2103-2114. [Cross Ref] [Pub Med].
89. Jacobson, M.D.;Weil, M.; Raff, M.C. Programmed cell death in animal development. Cell 1997, 88, 347-354. [Cross Ref].
90. Lowe, S.W.; Lin, A.W. Apoptosis in cancer. Carcinogenesis 2000, 21, 485-495. [Cross Ref] [Pub Med].
91. Chien, S.Y.; Wu, Y.C.; Chung, J.G.; Yang, J.S.; Lu, H.F.; Tsou, M.F.; Wood, W.G.; Kuo, S.J.; Chen, D.R. Quercetin-induced apoptosis acts through mitochondrial- And caspase-3-dependent pathways in human breast cancer MDA-MB-231 cells. Hum. Exp. Toxicol. 2009, 28, 493-503. [CrossRef] [PubMed].
92. Kim, H.J.; Kim, S.K.; Kim, B.S.; Lee, S.H.; Park, Y.S.; Park, B.K.; Kim, S.J.; Kim, J.; Choi, C.; Kim, J.S.; et al. Apoptotic effect of quercetin on HT-29 colon cancer cells via the AMPK signaling pathway. J. Agric. Food Chem. 2010, 58, 8643-8650. [Cross Ref] [Pub Med].
93. Seo, H.S.; Ju, J.H.; Jang, K.; Shin, I. Induction of apoptotic cell death by phytoestrogens by up-regulating the levels of phospho-p53 and p21 in normal and malignant estrogen receptor alpha-negative breast cells. Nutr. Res. 2011, 31, 139-146. [Cross Ref] [Pub Med].
94. p53-independent manner. Int. J. Mol. Med. 2014, 33, 863-869. [Cross Ref] [Pub Med].
95. Duo, J.; Ying, G.G.; Wang, G.W.; Zhang, L. Quercetin inhibits human breast cancer cell proliferation and induces apoptosis via Bcl-2 and Bax regulation. Mol. Med. Rep. 2012, 5, 1453-1456. [Pub Med].
96. Lee, D.H.; Lee, Y.J. Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) through inhibiting protein synthesis. J. Cell. Biochem. 2008, 105, 546-553. [Cross Ref] [Pub Med].
97. Ranganathan, S.; Halagowder, D.; Sivasithambaram, N.D. Quercetin Suppresses Twist to Induce Apoptosis in MCF-7 Breast Cancer Cells. Plos One 2015, 10, e0141370. [Cross Ref] [Pub Med].
98. Bhat, F.A.; Sharmila, G.; Balakrishnan, S.; Arunkumar, R.; Elumalai, P.; Suganya, S.; Raja Singh, P.; Srinivasan, N.; Arunakaran, J. Quercetin reverses EGF-induced epithelial to mesenchymal transition and invasiveness in prostate cancer (PC-3) cell line via EGFR/PI3K/Akt pathway. J. Nutr. Biochem. 2014, 25, 1132-1139. [Cross Ref] [Pub Med].
99. Maurya, A.K.; Vinayak, M. Modulation of PKC signaling and induction of apoptosis through suppression of reactive oxygen species and tumor necrosis factor receptor 1 (TNFR1): Key role of quercetin in cancer prevention. Tumour Biol. 2015, 36, 8913-8924. [Cross Ref] [Pub Med].
100. Sun, Z.J.; Chen, G.; Hu, X.; Zhang, W.; Liu, Y.; Zhu, L.X.; Zhou, Q.; Zhao, Y.F. Activation of PI3K/Akt/IKK-alpha/NF-kappaB signaling pathway is required for the apoptosis-evasion in human salivary adenoid cystic carcinoma: Its inhibition by quercetin. Apoptosis 2010, 15, 850-863. [CrossRef] [PubMed].
101. Yi, L.; Zongyuan, Y.; Cheng, G.; Lingyun, Z.; Guilian, Y.;Wei, G. Quercetin enhances apoptotic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in ovarian cancer cells through reactive oxygen species (ROS) mediated CCAAT enhancer-binding protein homologous protein (CHOP)-death receptor 5 pathway. Cancer Sci. 2014, 105, 520-527. [Cross Ref] [Pub Med].
102. Bishayee, K.; Ghosh, S.; Mukherjee, A.; Sadhukhan, R.; Mondal, J.; Khuda-Bukhsh, A.R. Quercetin induces cytochrome-c release and ROS accumulation to promote apoptosis and arrest the cell cycle in G2/M, in cervical carcinoma: Signal cascade and drug-DNA interaction. Cell Prolif. 2013, 46, 153-163. [Cross Ref] [Pub Med].
103. Bi, Y.; Shen, C.; Li, C.; Liu, Y.; Gao, D.; Shi, C.; Peng, F.; Liu, Z.; Zhao, B.; Zheng, Z.; et al. Inhibition of autophagy induced by quercetin at a late stage enhances cytotoxic effects on glioma cells. Tumour Biol. 2015. [Cross Ref] [Pub Med].
104. Kim, H.; Moon, J.Y.; Ahn, K.S.; Cho, S.K. Quercetin induces mitochondrial mediated apoptosis and protective autophagy in human glioblastoma U373MG cells. Oxid. Med. Cell. Longev. 2013, 2013, 596496. [Cross Ref] [Pub Med].
105. Hudson, S.P.; Padera, R.F.; Langer, R.; Kohane, D.S. The biocompatibility of mesoporous silicates. Biomaterials 2008, 29, 4045-4055. [Cross Ref] [Pub Med].
106. Ambrogio, M.W.; Thomas, C.R.; Zhao, Y.L.; Zink, J.I.; Stoddart, J.F. Mechanized silica nanoparticles: A new frontier in theranostic nanomedicine. Acc. Chem. Res. 2011, 44, 903-913. [Cross Ref] [Pub Med].
107. Fontecave, T.; Sanchez, C.; Azaïs, T.; Boissière, C. Chemical modification as a versatile tool for tuning stability of silica based mesoporous carriers in biologically relevant conditions. Chem. Mater. 2012, 24, 4326-4336. [Cross Ref].
108. Wang, Y.; Zhao, Q.; Han, N.; Bai, L.; Li, J.; Liu, J.; Che, E.; Hu, L.; Zhang, Q.; Jiang, T.;Wang, S. Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomed. Nanotechnol. Biol. Med. 2015, 11, 313-327. [Cross Ref] [Pub Med].
109. Andersson, J.; Rosenholm, J.; Areva, S.; Lindén, M. Influences of material characteristics on ibuprofen drug loading and release profiles from ordered micro- And mesoporous silica matrices. Chem. Mater. 2004, 16, 4160-4167. [Cross Ref].
110. Hu, Y.; Zhi, Z.; Zhao, Q.; Wu, C.; Zhao, P.; Jiang, H.; Jiang, T.; Wang, S. 3D cubic mesoporous silica microsphere as a carrier for poorly soluble drug carvedilol. Microporous Mesoporous Mater. 2012, 147, 94-101. [Cross Ref].
111. Souris, J.S.; Lee, C.H.; Cheng, S.H.; Chen, C.T.; Yang, C.S.; Ho, J.A.; Mou, C.Y.; Lo, L.W. Surface charge-mediated rapid hepatobiliary excretion of mesoporous silica nanoparticles. Biomaterials 2010, 31, 5564-5574. [Cross Ref] [Pub Med].
112. Lu, J.; Liong, M.; Li, Z.; Zink, J.I.; Tamanoi, F. Biocompatibility, biodistribution, and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals. Small 2010, 6, 1794-1805. [Cross Ref] [Pub Med].
113. Zhang, Y.; Wang, J.; Bai, X.; Jiang, T.; Zhang, Q.; Wang, S. Mesoporous silica nanoparticles for increasing the oral bioavailability and permeation of poorly water soluble drugs. Mol. Pharm. 2012, 9, 505-513. [Cross Ref] [Pub Med].
114. Ahern, R.J.; Hanrahan, J.P.; Tobin, J.M.; Ryan, K.B.; Crean, A.M. Comparison of fenofibrate-mesoporous silica drug-loading processes for enhanced drug delivery. Eur. J. Pharm. Sci. 2013, 50, 400-409. [Cross Ref] [Pub Med].
115. Zhang, Y.; Jiang, T.; Zhang, Q.; Wang, S. Inclusion of telmisartan in mesocellular foam nanoparticles: Drug loading and release property. Eur. J. Pharm. Biopharm. 2010, 76, 17-23. [Cross Ref] [Pub Med].
116. Michelina, C.; Ferdinando, P.; Flavia, B.; Simona, P.; Sabina, M.; Paola, N.; Severina, P. Silica/quercetin sol-gel hybrids as antioxidant dental implant materials. Sci. Technol. Adv. Mater. 2015, 16, 035001.
117. Sapino, S.; Ugazio, E.; Gastaldi, L.; Miletto, I.; Berlier, G.; Zonari, D.; Oliaro-Bosso, S. Mesoporous silica as topical nanocarriers for quercetin: Characterization and in vitro studies. Eur. J. Pharm. Biopharm. 2015, 89, 116-125. [Cross Ref] [Pub Med].
118. Tang, L.; Cheng, J. Nonporous silica nanoparticles for nanomedicine application. Nano Today 2013, 8, 290-312. [Cross Ref] [Pub Med].
119. Benezra, M.; Penate-Medina, O.; Zanzonico, P.B.; Schaer, D.; Ow, H.; Burns, A.; DeStanchina, E.; Longo, V.; Herz, E.; Iyer, S.; et al. Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma. J. Clin. Investig. 2011, 121, 2768-2780. [Cross Ref] [Pub Med].
120. Bradbury, M.S.; Phillips, E.; Montero, P.H.; Cheal, S.M.; Stambuk, H.; Durack, J.C.; Sofocleous, C.T.; Meester, R.J.; Wiesner, U.; Patel, S. Clinically-translated silica nanoparticles as dual-modality cancer-targeted probes for image-guided surgery and interventions. Integr. Biol. 2013, 5, 74-86. [Cross Ref] [Pub Med].
121. Danhier, F.; Ansorena, E.; Silva, J.M.; Coco, R.; le Breton, A.; Preat, V. PLGA-based nanoparticles: An overview of biomedical applications. J. Control Release 2012, 161, 505-522. [Cross Ref] [Pub Med].
122. Asghar, W.; Islam, M.; Wadajkar, A.S.; Yuan, W.; Ilyas, A.; Nguyen, K.T.; Iqbal, S.M. PLGA Micro- And Nanoparticles Loaded Into Gelatin Scaffold for Controlled Drug Release. IEEE Trans. Nanotechnol. 2012, 11, 546-553. [Cross Ref].
123. Hussein, A.S.; Abdullah, N.; Ahmadun, F.R. In vitro degradation of poly (D, L-lactide-co-glycolide) nanoparticles loaded with linamarin. IET Nanobiotechnol. 2013, 7, 33-41. [Cross Ref] [Pub Med].
124. Gratton, S.E.; Ropp, P.A.; Pohlhaus, P.D.; Luft, J.C.; Madden, V.J.; Napier, M.E.; DeSimone, J.M. The effect of particle design on cellular internalization pathways. Proc. Natl. Acad. Sci. USA 2008, 105, 11613-11618. [Cross Ref] [Pub Med].
125. Pimple, S.; Manjappa, A.S.; Ukawala, M.; Murthy, R.S. PLGA nanoparticles loaded with etoposide and quercetin dihydrate individually: In vitro cell line study to ensure advantage of combination therapy. Cancer Nanotechnol. 2012, 3, 25-36. [Cross Ref] [Pub Med].
126. Pandey, S.K.; Patel, D.K.; Thakur, R.; Mishra, D.P.; Maiti, P.; Haldar, C. Anti-cancer evaluation of quercetin embedded PLA nanoparticles synthesized by emulsified nanoprecipitation. Int. J. Biol. Macromol. 2015, 75, 521-529. [Cross Ref] [Pub Med].
127. Pool, H.; Quintanar, D.; de Figueroa, J.D.; Mano, C.M.; Bechara, J.E. H.; Godinez, L.A.; Mendoza, S. Antioxidant effects of quercetin and catechin encapsulated into PLGA nanoparticles. J. Nanomater. 2012, 2012. [Cross Ref].
128. p53-ROS crosstalk to induce apoptosis in hepatocarcinoma cells. Mol. Cells 2015, 38, 518-527. [Cross Ref] [Pub Med].
129. Jain, A.K.; Thanki, K.; Jain, S. Co-encapsulation of tamoxifen and quercetin in polymeric nanoparticles: Implications on oral bioavailability, antitumor efficacy, and drug-induced toxicity. Mol. Pharm. 2013, 10, 3459-3474. [Cross Ref] [Pub Med].
130. El-Gogary, R.I.; Rubio, N.;Wang, J.T.-W.; Al-Jamal, W.T.; Bourgognon, M.; Kafa, H.; Naeem, M.; Klippstein, R.; Abbate, V.; Leroux, F.; et al. Polyethylene glycol conjugated polymeric nanocapsules for targeted delivery of quercetin to folate-expressing cancer cells in vitro and in vivo. ACS Nano 2014, 8, 1384-1401. [Cross Ref] [Pub Med].
131. Sharma, G.; Park, J.; Sharma, A.R.; Jung, J.S.; Kim, H.; Chakraborty, C.; Song, D.K.; Lee, S.S.; Nam, J.S. Methoxy poly(ethylene glycol)-poly(lactide) nanoparticles encapsulating quercetin act as an effective anticancer agent by inducing apoptosis in breast cancer. Pharm. Res. 2015, 32, 723-735. [Cross Ref] [Pub Med].
132. Kumari, A.; Kumar, V.; Yadav, S.K. Plant extract synthesized PLA nanoparticles for controlled and sustained release of quercetin: A green approach. PLoS ONE 2012, 7, e41230. [CrossRef] [PubMed].
133. Ravi Kumar, M.N.V. A review of chitin and chitosan applications. React. Funct. Polym. 2000, 46, 1-27. [Cross Ref].
134. Huang, M.; Khor, E.; Lim, L.Y. Uptake and cytotoxicity of chitosan molecules and nanoparticles: Effects of molecular weight and degree of deacetylation. Pharm. Res. 2004, 21, 344-353. [Cross Ref] [Pub Med].
135. Ma, Z.; Lim, T.M.; Lim, L.Y. Pharmacological activity of peroral chitosan-insulin nanoparticles in diabetic rats. Int. J. Pharm. 2005, 293, 271-280. [Cross Ref] [Pub Med].
136. Smith, J.M.; Dornish, M.; Wood, E.J. Involvement of protein kinase C in chitosan glutamate-mediated tight junction disruption. Biomaterials 2005, 26, 3269-3276. [Cross Ref] [Pub Med].
137. Qiao, Y.; Bai, X.F.; Du, Y.G. Chitosan oligosaccharides protect mice from LPS challenge by attenuation of inflammation and oxidative stress. Int. Immunopharmacol. 2011, 11, 121-127. [Cross Ref] [Pub Med].
138. Liu, H.T.; Li, W.M.; Xu, G.; Li, X.Y.; Bai, X.F.; Wei, P.; Yu, C.; Du, Y.G. Chitosan oligosaccharides attenuate hydrogen peroxide-induced stress injury in human umbilical vein endothelial cells. Pharmacol. Res. 2009, 59, 167-175. [Cross Ref] [Pub Med].
139. Singla, A.K.; Chawla, M. Chitosan: Some pharmaceutical and biological aspects-An update. J. Pharm. Pharmacol. 2001, 53, 1047-1067. [Cross Ref] [Pub Med].
140. Sonvico, F.; Cagnani, A.; Rossi, A.; Motta, S.; di Bari, M.T.; Cavatorta, F.; Alonso, M.J.; Deriu, A.; Colombo, P. Formation of self-organized nanoparticles by lecithin/chitosan ionic interaction. Int. J. Pharm. 2006, 324, 67-73. [Cross Ref] [Pub Med].
141. Raj, L.F.A.A.; Jonisha, R.; Revathi, B.; Jayalakshmy, E. Preparation and characterization of BSA and chitosan nanopartices for sustainable delivery system for quercetin. J. Appl. Pharm. Sci. 2015, 5, 1-5. [Cross Ref].
142. Sonaje, K.; Lin, K.J.; Tseng, M.T.;Wey, S.P.; Su, F.Y.; Chuang, E.Y.; Hsu, C.W.; Chen, C.T.; Sung, H.W. Effects of chitosan-nanoparticle-mediated tight junction opening on the oral absorption of endotoxins. Biomaterials 2011, 32, 8712-8721. [Cross Ref] [Pub Med].
143. Feng, C.; Wang, Z.; Jiang, C.; Kong, M.; Zhou, X.; Li, Y.; Cheng, X.; Chen, X. Chitosan/O-carboxymethyl chitosan nanoparticles for efficient and safe oral anticancer drug delivery: In vitro and in vivo evaluation. Int. J. Pharm. 2013, 457, 158-167. [Cross Ref] [Pub Med].
144. David, K.I.; Jaidev, L.R.; Sethuraman, S.; Krishnan, U.M. Dual drug loaded chitosan nanoparticles-sugar-coated arsenal against pancreatic cancer. Colloids Surf. B Biointerfaces 2015, 135, 689-698. [Cross Ref] [Pub Med].
145. Choi, J.S.; Jo, B.W.; Kim, Y.C. Enhanced paclitaxel bioavailability after oral administration of paclitaxel or prodrug to rats pretreated with quercetin. Eur. J. Pharm. Biopharm. 2004, 57, 313-318. [Cross Ref] [Pub Med].
146. Wang, X.; Chen, Y.; Dahmani, F.Z.; Yin, L.; Zhou, J.; Yao, J. Amphiphilic carboxymethyl chitosan-quercetin conjugate with P-gp inhibitory properties for oral delivery of paclitaxel. Biomaterials 2014, 35, 7654-7665. [Cross Ref] [Pub Med].
147. Torchilin, V.P. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov. 2005, 4, 145-160. [Cross Ref] [Pub Med].
148. Kundu, S.K.; Sharma, A.R.; Lee, S.S.; Sharma, G.; Doss, C.G.; Yagihara, S.; Kim, D.Y.; Nam, J.S.; Chakraborty, C. Recent trends of polymer mediated liposomal gene delivery system. Biomed. Res. Int. 2014, 2014, 934605. [Cross Ref] [Pub Med].
149. Yuan, F.; Dellian, M.; Fukumura, D.; Leunig, M.; Berk, D.A.; Torchilin, V.P.; Jain, R.K. Vascular permeability in a human tumor xenograft: Molecular size dependence and cutoff size. Cancer Res. 1995, 55, 3752-3756. [Pub Med].
150. Stone, W.L.; Smith, M. Therapeutic uses of antioxidant liposomes. Mol. Biotechnol. 2004, 27, 217-230. [Cross Ref].
151. Zhang, L.; Gu, F.X.; Chan, J.M.; Wang, A.Z.; Langer, R.S.; Farokhzad, O.C. Nanoparticles in medicine: Therapeutic applications and developments. Clin. Pharmacol. Ther. 2008, 83, 761-769. [Cross Ref] [Pub Med].
152. Wang, G.; Wang, J.J.; Yang, G.Y.; Du, S.M.; Zeng, N.; Li, D.S.; Li, R.M.; Chen, J.Y.; Feng, J.B.; Yuan, S.H.; et al. Effects of quercetin nanoliposomes on C6 glioma cells through induction of type III programmed cell death. Int. J. Nanomed. 2012, 7, 271-280.
153. Rezaei-Sadabady, R.; Eidi, A.; Zarghami, N.; Barzegar, A. Intracellular ROS protection efficiency and free radical-scavenging activity of quercetin and quercetin-encapsulated liposomes. Artif. Cells Nanomed. Biotechnol. 2014, 24, 1-7. [Cross Ref] [Pub Med].
154. Dian, L.; Yu, E.; Chen, X.; Wen, X.; Zhang, Z.; Qin, L.; Wang, Q.; Li, G.; Wu, C. Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles. Nanoscale Res. Lett. 2014, 9. [Cross Ref] [Pub Med].
155. Tan, B.J.; Liu, Y.; Chang, K.L.; Lim, B.K.; Chiu, G.N. Perorally active nanomicellar formulation of quercetin in the treatment of lung cancer. Int. J. Nanomed. 2012, 7, 651-661.
156. Han, Q.; Yang, R.; Li, J.; Liang, W.; Zhang, Y.; Dong, M.; Besenbacher, F.; Wang, C. Enhancement of biological activities of nanostructured hydrophobic drug species. Nanoscale 2012, 4, 2078-2082. [Cross Ref] [Pub Med].
157. Li, C.; Zhang, J.; Zu, Y.J.; Nie, S.F.; Cao, J.; Wang, Q.; Nie, S.P.; Deng, Z.Y.; Xie, M.Y.; Wang, S. Biocompatible and biodegradable nanoparticles for enhancement of anti-cancer activities of phytochemicals. Chin. J. Nat. Med. 2015, 13, 641-652. [Cross Ref].
158. Nair, H.B.; Sung, B.; Yadav, V.R.; Kannappan, R.; Chaturvedi, M.M.; Aggarwal, B.B. Delivery of antiinflammatory nutraceuticals by nanoparticles for the prevention and treatment of cancer. Biochem. Pharmacol. 2010, 80, 1833-1843. [Cross Ref] [Pub Med].
159. Santos, I.S.; Ponte, B.M.; Boonme, P.; Silva, A.M.; Souto, E.B. Nanoencapsulation of polyphenols for protective effect against colon-rectal cancer. Biotechnol. Adv. 2013, 31, 514-523. [Cross Ref] [Pub Med].
160. Sanna, V.; Siddiqui, I.A.; Sechi, M.; Mukhtar, H. Nanoformulation of natural products for prevention and therapy of prostate cancer. Cancer Lett. 2013, 334, 142-151. [Cross Ref] [Pub Med].
161. Parveen, S.; Misra, R.; Sahoo, S.K. Nanoparticles: A boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine 2012, 8, 147-166. [Cross Ref] [Pub Med].
162. Sun, M.; Nie, S.; Pan, X.; Zhang, R.; Fan, Z.; Wang, S. Quercetin-nanostructured lipid carriers: Characteristics and anti-breast cancer activities in vitro. Colloids Surf. B Biointerfaces 2014, 113, 15-24. [Cross Ref] [Pub Med].