Evidence available from nutritional epidemiology has indicated an inverse association between regular consumption of fruits and vegetables and the risk of developing certain types of cancer. In turn, preclinical studies have attributed the health-promoting effects of plant foods to some groups of phytochemicals, by virtue of their many biological activities. In this survey, we briefly examine the chemopreventive potential of flavonoids and flavonoid-rich foods in human oral carcinogenesis. Despite the paucity of data from clinical trials and epidemiological studies, in comparison to in vitro/ in vivo investigations, a high level of evidence has been reported for epigallocatechin gallate (EGCG) and anthocyanins. These flavonoids, abundant in green tea and black raspberries, respectively, represent promising chemopreventive agents in human oral cancer.
References
[1]
Lucenteforte, E.; Garavello, W.; Bosetti, C.; La Vecchia, C. Dietary factors and oral and pharyngeal cancer risk. Oral Oncol. 2009, 45, 461–467, doi:10.1016/j.oraloncology.2008.09.002.
[2]
Estruch, R.; Ros, E.; Salas-Salvadó, J.; Covas, M.I.; Corella, D.; Arós, F.; Gómez-Gracia, E.; Ruiz-Gutiérrez, V.; Fiol, M.; Lapetra, J.; et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N. Engl. J. Med. 2013, 368, 1279–1290, doi:10.1056/NEJMoa1200303.
[3]
Iriti, M.; Faoro, F. Bioactivity of grape chemicals for human health. Nat. Prod. Commun. 2009, 4, 611–634.
[4]
Iriti, M.; Faoro, F. Chemical diversity and defence metabolism: How plants cope with pathogens and ozone pollution. Int. J. Mol. Sci. 2009, 10, 3371–3399, doi:10.3390/ijms10083371.
[5]
Iriti, M.; Faoro, F. Plant defense and human nutrition: Phenylpropanoids on the menu. Curr. Top. Nutr. Res. 2004, 2, 47–65.
[6]
Iriti, M. Introduction to polyphenols, plant chemicals for human health. Mini-Rev. Med. Chem. 2011, 11, 1183–1185.
[7]
Petersen, P.E. Oral cancer prevention and control? The approach of the World Health Organization. Oral Oncol. 2009, 45, 454–460.
[8]
Siegel, R.; Naishadham, D.; Jemal, A. Cancer statistics, 2013. CA Cancer J. Clin. 2013, 63, 11–30, doi:10.3322/caac.21166.
[9]
Tanaka, T.; Tanaka, M.; Tanaka, T. Oral carcinogenesis and oral cancer chemoprevention: A review. Pathol. Res. Int. 2011, 2011, doi:10.4061/2011/431246.
[10]
Carnelio, S.; Rodrigues, G.S.; Shenoy, R.; Fernandes, D. A brief review of common oral premalignant lesions with emphasis on their management and cancer prevention. Indian J. Surg. 2011, 73, 256–261, doi:10.1007/s12262-011-0286-6.
[11]
Lodi, G.; Franchini, R.; Bez, C.; Sardella, A.; Moneghini, L.; Pellegrini, C.; Bosari, S.; Manfredi, M.; Vescovi, P.; Carrassi, A. Detection of survivin mRNA in healthy oral mucosa, oral leucoplakia and oral cancer. Oral Dis. 2010, 16, 61–67, doi:10.1111/j.1601-0825.2009.01614.x.
[12]
Lodi, G.; Carrozzo, M.; Furness, S.; Thongprasom, K. Interventions for treating oral lichen planus: A systematic review. Br. J. Dermatol. 2012, 166, 938–947, doi:10.1111/j.1365-2133.2012.10821.x.
[13]
Syrj？nen, S.; Lodi, G.; von Bültzingsl？wen, I.; Aliko, A.; Arduino, P.; Campisi, G.; Challacombe, S.; Ficarra, G.; Flaitz, C.; Zhou, H.M.; et al. Human papillomaviruses in oral carcinoma and oral potentially malignant disorders: A systematic review. Oral Dis. 2011, 17 (Suppl. 1), 58–72.
[14]
Surh, Y.J. Cancer chemoprevention with dietary phytochemicals. Nat. Rev. Cancer 2003, 3, 768–780, doi:10.1038/nrc1189.
[15]
De Moura, C.F.; Noguti, J.; de Jesus, G.P.; Ribeiro, F.A.; Garcia, F.A.; Gollucke, A.P.; Aguiar, O., Jr.; Ribeiro, D.A. Polyphenols as a chemopreventive agent in oral carcinogenesis: Putative mechanisms of action using in-vitro and in-vivo test systems. Eur. J. Cancer Prev. 2012, doi:10.1097/CEJ.0b013e32835b6a94.
[16]
Varoni, E.M.; Lodi, G.; Sardella, A.; Carrassi, A.; Iriti, M. Plant polyphenols and oral health: Old phytochemicals for new fields. Curr. Med. Chem. 2012, 19, 1706–1720, doi:10.2174/092986712799945012.
[17]
Johnson, T.L.; Lai, M.B.; Lai, J.C.; Bhushan, A. Inhibition of cell proliferation and MAP kinase and Akt pathways in oral squamous cell carcinoma by genistein and biochanin A. Evid. Based Complement. Altern. Med. 2010, 7, 351–358, doi:10.1093/ecam/nen011.
[18]
Cheng, Y.H.; Li, L.A.; Lin, P.; Cheng, L.C.; Hung, C.H.; Chang, N.W.; Lin, C. Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation. Toxicol. Appl. Pharmacol. 2012, 263, 360–367, doi:10.1016/j.taap.2012.07.010.
[19]
Chen, S.F.; Nien, S.; Wu, C.H.; Liu, C.L.; Chang, Y.C.; Lin, Y.S. Reappraisal of the anticancer efficacy of quercetin in oral cancer cells. J. Chin. Med. Assoc. 2013, 76, 146–152, doi:10.1016/j.jcma.2012.11.008.
[20]
Yang, S.H.; Liao, P.H.; Pan, Y.F.; Chen, S.L.; Chou, S.S.; Chou, M.Y. The novel p53-dependent metastatic and apoptotic pathway induced by vitexin in human oral cancer OC2 cells. Phytother. Res. 2012, doi:10.1002/ptr.4841.
[21]
Silvan, S.; Manoharan, S.; Baskaran, N.; Anusuya, C.; Karthikeyan, S.; Prabhakar, M.M. Chemopreventive potential of apigenin in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis. Eur. J. Pharmacol. 2011, 670, 571–577, doi:10.1016/j.ejphar.2011.09.179.
[22]
Gómez-García, F.J.; López-Jornet, M.P.; álvarez-Sánchez, N.; Castillo-Sánchez, J.; Benavente-García, O.; Vicente Ortega, V. Effect of the phenolic compounds apigenin and carnosic acid on oral carcinogenesis in hamster induced by DMBA. Oral Dis. 2013, 19, 279–286.
[23]
Kim, J.W.; Amin, A.R.; Shin, D.M. Chemoprevention of head and neck cancer with green tea polyphenols. Cancer Prev. Res. 2010, 3, 900–909, doi:10.1158/1940-6207.CAPR-09-0131.
[24]
Lee, U.L.; Choi, S.W. The chemopreventive properties and therapeutic modulation of green tea polyphenols in oral squamous cell carcinoma. ISRN Oncol. 2011, 2011, doi:10.5402/2011/403707.
[25]
Narotzki, B.; Reznick, A.Z.; Aizenbud, D.; Levy, Y. Green tea: A promising natural product in oral health. Arch. Oral Biol. 2012, 57, 429–435.
[26]
Winn, D.M.; Ziegler, R.G.; Pickle, L.W.; Gridley, G.; Blot, W.J.; Hoover, R.N. Diet in the etiology of oral and pharyngeal cancer among women from the southern United States. Cancer Res. 1984, 44, 1216–1222.
[27]
Chuang, S.C.; Jenab, M.; Heck, J.E.; Bosetti, C.; Talamini, R.; Matsuo, K.; Castellsague, X.; Franceschi, S.; Herrero, R.; Winn, D.M.; et al. Diet and the risk of head and neck cancer: A pooled analysis in the INHANCE consortium. Cancer Causes Control 2011, 23, 69–88.
[28]
De Stefani, E.; Ronco, A.L.; Mendilaharsu, M.; Deneo-Pellegrini, H. Diet and risk of cancer of the upper aerodigestive tract—II. Nutrients. Oral Oncol. 1999, 35, 22–26, doi:10.1016/S1368-8375(98)00061-X.
[29]
Rossi, M.; Garavello, W.; Talamini, R.; Negri, E.; Bosetti, C.; Dal Maso, L.; Lagiou, P.; Tavani, A.; Polesel, J.; Barzan, L.; et al. Flavonoids and the risk of oral and pharyngeal cancer: A case-control study from Italy. Cancer Epidemiol. Biomark. Prev. 2007, 16, 1621–1625, doi:10.1158/1055-9965.EPI-07-0168.
[30]
Ide, R.; Fujino, Y.; Hoshiyama, Y.; Mizoue, T.; Kubo, T.; Pham, T.M.; Shirane, K.; Tokui, N.; Sakata, K.; Tamakoshi, A.; et al. A prospective study of green tea consumption and oral cancer incidence in Japan. Ann. Epidemiol. 2007, 17, 821–826, doi:10.1016/j.annepidem.2007.04.003.
[31]
Hildebrand, J.S.; Patel, A.V.; McCullough, M.L.; Gaudet, M.M.; Chen, A.Y.; Hayes, R.B.; Gapstur, S.M. Coffee, tea, and fatal oral/pharyngeal cancer in a large prospective US cohor. Am. J. Epidemiol. 2013, 177, 50–58, doi:10.1093/aje/kws222.
[32]
Sang, S.; Lambert, J.D.; Ho, C.T.; Yang, C.S. The chemistry and biotransformation of tea constituents. Pharmacol. Res. 2011, 64, 87–99, doi:10.1016/j.phrs.2011.02.007.
[33]
Rado？, L.; Paget-Bailly, S.; Menvielle, G.; Cyr, D.; Schmaus, A.; Carton, M.; Guida, F.; Cénée, S.; Sanchez, M.; Guizard, A.V.; et al. Tea and coffee consumption and risk of oral cavity cancer: Results of a large population-based case-control study, the ICARE study. Cancer Epidemiol. 2013, 37, 284–289, doi:10.1016/j.canep.2013.02.001.
[34]
Boehm, K.; Borrelli, F.; Ernst, E.; Habacher, G.; Hung, S.K.; Milazzo, S.; Horneber, M. Green tea (Camellia sinensis) for the prevention of cancer. Cochrane Database Syst. Rev. 2009, doi:10.1002/14651858.CD005004.pub2.
[35]
Li, N.; Sun, Z.; Han, C.; Chen, J. The chemopreventive effects of tea on human oral precancerous mucosa lesions. Proc. Soc. Exp. Biol. Med. 2003, 220, 218–224.
[36]
Schwartz, J.L.; Baker, V.; Larios, E.; Chung, F.L. Molecular and cellular effects of green tea on oral cells of smokers: A pilot study. Mol. Nutr. Food Res. 2005, 49, 43–51, doi:10.1002/mnfr.200400031.
[37]
Tsao, A.S.; Liu, D.; Martin, J.; Tang, X.M.; Lee, J.J.; El-Naggar, A.K.; Wistuba, I.; Culotta, K.S.; Mao, L.; Gillenwater, A.; et al. Phase II randomized, placebo-controlled trial of green tea extract in patients with high-risk oral premalignant lesions. Cancer Prev. Res. 2009, 2, 931–941, doi:10.1158/1940-6207.CAPR-09-0121.
[38]
Yoon, A.J.; Shen, J.; Santella, R.M.; Philipone, E.M.; Wu, H.C.; Eisig, S.B.; Blitzer, A.; Close, L.G.; Zegarelli, D.J. Topical application of green tea polyphenol (？)-epigallocatechin-3-gallate (EGCG) for prevention of recurrent oral neoplastic lesions. J. Orofac. Sci. 2012, 4, 43–50.
[39]
Chow, H.H.S.; Hakim, I.A. Pharmacokinetic and chemoprevention studies on tea in humans. Pharmacol. Res. 2011, 64, 105–112.
[40]
Manach, C.; Williamson, G.; Morand, C.; Scalbert, A.; Rémésy, C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am. J. Clin. Nutr. 2005, 81, 230S–242S.
[41]
Scheepens, A.; Tan, K.; Paxton, J.W. Improving the oral bioavailability of beneficial polyphenols through designed synergies. Genes Nutr. 2010, 5, 75–87, doi:10.1007/s12263-009-0148-z.
[42]
Walle, T.; Browning, A.M.; Steed, L.L.; Reed, S.G.; Walle, U.K. Flavonoid glucosides are hydrolyzed and thus activated in the oral cavity in humans. J. Nutr. 2005, 135, 48–52.
[43]
Mallery, S.R.; Budendorf, D.E.; Larsen, M.P.; Pei, P.; Tong, M.; Holpuch, A.S.; Larsen, P.E.; Stoner, G.D.; Fields, H.W.; Chan, K.K.; et al. Effects of human oral mucosal tissue, saliva, and oral microflora on intraoral metabolism and bioactivation of black raspberry anthocyanins. Cancer Prev. Res. 2011, 4, 1209–1221, doi:10.1158/1940-6207.CAPR-11-0040.
[44]
Siddiqui, I.A.; Mukhtar, H. Nanochemoprevention by bioactive food components: A perspective. Pharm. Res. 2010, 27, 1054–1060, doi:10.1007/s11095-010-0087-9.
[45]
Siddiqui, I.A.; Adhami, V.M.; Christopher, J. Impact of nanotechnology in cancer: Emphasis on nanochemoprevention. Int. J. Nanomed. 2012, 7, 591–605.
[46]
Siddiqui, I.A.; Adhami, V.M.; Bharali, D.J.; Hafeez, B.B.; Asim, M.; Khwaja, S.I.; Ahmad, N.; Cui, H.; Mousa, S.A.; Mukhtar, H. Introducing nanochemoprevention as a novel approach for cancer control: Proof of principle with green tea polyphenol epigallocatechin-3-gallate. Cancer Res. 2009, 69, 1712–1716, doi:10.1158/0008-5472.CAN-08-3978.
Satheesh Madhav, N.V.; Semwal, R.; Semwal, D.K.; Semwal, R.B. Recent trends in oral transmucosal drug delivery systems: An emphasis on the soft palatal route. Exp. Opin. Drug Deliv. 2012, 9, 629–647, doi:10.1517/17425247.2012.679260.
[49]
Senel, S.; Rathbone, M.J.; Cansiz, M.; Pather, I. Recent developments in buccal and sublingual delivery systems. Exp. Opin. Drug Deliv. 2012, 9, 615–628, doi:10.1517/17425247.2012.676040.
[50]
Holpuch, A.S.; Desai, K.H.; Schwendeman, S.P.; Mallery, S.R. Optimizing therapeutic efficacy of chemopreventive agents: A critical review of delivery strategies in oral cancer chemoprevention clinical trials. J. Carcinog. 2011, 10, 23, doi:10.4103/1477-3163.85185.
[51]
Wu, X.; Desai, K.G.H.; Mallery, S.R.; Holpuch, A.S.; Phelps, M.P.; Schwendeman, S.P. Mucoadhesive fenretinide patches for site-specific chemoprevention of oral cancer: Enhancement of oral mucosal permeation of fenretinide by coincorporation of propylene glycol and menthol. Mol. Pharm. 2012, 9, 937–945.
[52]
Ling, Y.; Ren, C.; Mallery, S.R.; Ugalde, C.M.; Pei, P.; Saradhi, U.V.; Stoner, G.D.; Chan, K.K.; Liu, Z. A rapid and sensitive LC-MS/MS method for quantification of four anthocyanins and its application in a clinical pharmacology study of a bioadhesive black raspberry gel. J. Chromatogr. B 2009, 877, 4027–4034, doi:10.1016/j.jchromb.2009.10.026.
[53]
Ugalde, C.M.; Liu, Z.; Ren, C.; Chan, K.K.; Rodrigo, K.A.; Ling, Y.; Larsen, P.E.; Chacon, G.E.; Stoner, G.D.; Mumper, R.J.; et al. Distribution of anthocyanins delivered from a bioadhesive black raspberry gel following topical intraoral application in normal healthy volunteers. Pharm. Res. 2009, 26, 977–986, doi:10.1007/s11095-008-9806-x.
[54]
Shumway, B.S.; Kresty, L.A.; Larsen, P.E.; Zwick, J.C.; Lu, B.; Fields, H.W.; Mumper, R.J.; Stoner, G.D.; Mallery, S.R. Effects of a topically applied bioadhesive berry gel on loss of heterozygosity indices in premalignant oral lesions. Clin. Cancer Res. 2008, 14, 2421–2430, doi:10.1158/1078-0432.CCR-07-4096.
[55]
Mallery, S.R.; Zwick, J.C.; Pei, P.; Tong, M.; Larsen, P.E.; Shumway, B.S.; Lu, B.; Fields, H.W.; Mumper, R.J.; Stoner, G.D. Topical application of a bioadhesive black raspberry gel modulates gene expression and reduces cyclooxygenase 2 protein in human premalignant oral lesions. Cancer Res. 2008, 68, 4945–4957, doi:10.1158/0008-5472.CAN-08-0568.
