Chemoprevention of oral cancer by lyophilized strawberries.

BACKGROUND/AIM Oral cancer represents approximately 2.5% of all cancers in the United States, with five- and 10-year survival rates of 62% and 51%. In the present study, lyophilized strawberries (LS) were evaluated for their potential to inhibit tumorigenesis in the hamster cheek pouch (HCP) model of oral cancer and for their ability to modify expression of several genes relevant to oral cancer development. MATERIALS AND METHODS HCPs were painted three times a week for six weeks with 0.2% 7,12-dimethylbenz(a)anthracene (DMBA). Hamsters were given 5% or 10% LS in their diet prior to, during, and after, or only after carcinogen treatment. Animals were sacrificed 12 weeks from the beginning of DMBA treatment and the number of total lesions and tumors was determined. RESULTS A significant difference (p<0.01-0.04) in the number of tumors was found between the LS-treated groups and the carcinogen controls. Histological examination of HCPs revealed a significant reduction in mild and severe dysplasia following 12 weeks of treatment with LS. Molecular analysis revealed that genes related to tumor development were modulated by LS. CONCLUSION These experiments support previous studies in HCP that demonstrated a chemopreventive activity by black raspberries and show, to our knowledge for the first time, that strawberries can inhibit tumor formation in an animal model of oral cancer.

[1]  S. Fedele,et al.  The World Cancer Report and the burden of oral cancer. , 2004, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[2]  M. Quer,et al.  Second neoplasm in patients with head and neck cancer , 1999, Head & neck.

[3]  J. Chen,et al.  Tea preparations protect against DMBA-induced oral carcinogenesis in hamsters. , 1999, Nutrition and cancer.

[4]  D. Tromp,et al.  Oral and pharyngeal cancer: Analysis of patient delay at different tumor stages , 2005, Head & neck.

[5]  J L Buck,et al.  Tumors of the esophagus. , 1994, Seminars in roentgenology.

[6]  P. Rubin,et al.  Second malignancies in patients who have head and neck cancer: incidence, effect on survival and implications based on the RTOG experience. , 1989, International journal of radiation oncology, biology, physics.

[7]  K. Lee,et al.  The roles of polyphenols in cancer chemoprevention , 2006, BioFactors.

[8]  J. Skandalakis,et al.  Tumors of the Esophagus , 2000, World Journal of Surgery.

[9]  M. Ding,et al.  Inhibitory effect on activator protein-1, nuclear factor-kappaB, and cell transformation by extracts of strawberries (Fragaria x ananassa Duch.). , 2005, Journal of agricultural and food chemistry.

[10]  T. Iwasaki,et al.  Presence of a novel hamster oral papillomavirus in dysplastic lesions of hamster lingual mucosa induced by application of dimethylbenzanthracene and excisional wounding: molecular cloning and complete nucleotide sequence. , 1997, The Journal of general virology.

[11]  P. A. Maki,et al.  Effects of various preparations of dietary protease inhibitors on oral carcinogenesis in hamsters induced by DMBA. , 1993, Nutrition and cancer.

[12]  M. Pritts,et al.  Antioxidant and antiproliferative activities of strawberries. , 2003, Journal of agricultural and food chemistry.

[13]  K. Shah,et al.  Human papillomavirus–associated head and neck squamous cell carcinoma: mounting evidence for an etiologic role for human papillomavirus in a subset of head and neck cancers , 2001, Current opinion in oncology.

[14]  G. Shklar,et al.  Retardation of experimental oral cancer development by retinyl acetate. , 1983, Nutrition and cancer.

[15]  L. Garfinkel,et al.  Tobacco smoking, alcohol drinking, and cancer of the oral cavity and oropharynx among U.S. veterans , 1993, Cancer.

[16]  T. Slaga,et al.  Expression of epidermal growth factor receptor, polyamine levels, ornithine decarboxylase activity, micronuclei, and transglutaminase I in a 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis model. , 1990, Cancer research.

[17]  J. Schwartz,et al.  Regression of experimental oral carcinomas by local injection of beta-carotene and canthaxanthin. , 1988, Nutrition and cancer.

[18]  K. Karthikeyan,et al.  Chemopreventive effect of Ocimum sanctum on DMBA-induced hamster buccal pouch carcinogenesis. , 1999, Oral oncology.

[19]  P. Nourjah,et al.  U.S. adult knowledge of risk factors and signs of oral cancers: 1990. , 1995, Journal of the American Dental Association.

[20]  G. Thomas,et al.  Squamous cell cancer of the buccal mucosa in young adults. , 2004, The British journal of oral & maxillofacial surgery.

[21]  G. Stoner,et al.  Chemoprevention of esophageal tumorigenesis by dietary administration of lyophilized black raspberries. , 2001, Cancer research.

[22]  B. Casto,et al.  Chemoprevention by Fruit Phenolic Compounds , 2004 .

[23]  S. Oredsson,et al.  Antioxidant levels and inhibition of cancer cell proliferation in vitro by extracts from organically and conventionally cultivated strawberries. , 2006, Journal of agricultural and food chemistry.

[24]  G. Stoner,et al.  Protection Against Esophageal Cancer in Rodents With Lyophilized Berries: Potential Mechanisms , 2006, Nutrition and cancer.

[25]  Glade Mj.  Food, nutrition, and the prevention of cancer: a global perspective. American Institute for Cancer Research/World Cancer Research Fund, American Institute for Cancer Research, 1997. , 1999 .

[26]  C. Neto,et al.  p16INK4A Immunohistochemical Overexpression in Premalignant and Malignant Oral Lesions Infected with Human Papillomavirus , 2003, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[27]  C Yapijakis,et al.  The hamster model of sequential oral oncogenesis. , 2008, Oral Oncology.

[28]  D. Rimm,et al.  Prognostic Significance of p16 Protein Levels in Oropharyngeal Squamous Cell Cancer , 2004, Clinical Cancer Research.

[29]  D. Solt,et al.  Expression of the angiogenic phenotype by a subpopulation of keratinocytes derived from 7,12-dimethylbenz[a]anthracene-initiated hamster buccal pouch epithelium. , 1988, Carcinogenesis.

[30]  C. Weghorst,et al.  Mutational status of overexpressed p16 in head and neck cancer: evidence for germline mutation of p16/p14ARF. , 2002, International journal of oncology.

[31]  H. S. Scheuller,et al.  Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro. , 2006, Journal of agricultural and food chemistry.

[32]  V. Steele,et al.  Chemoprevention by lipoxygenase and leukotriene pathway inhibitors of vinyl carbamate-induced lung tumors in mice. , 2002, Cancer research.

[33]  P. O'Brien,et al.  Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. , 2004, Free radical biology & medicine.

[34]  Z. Husain,et al.  Sequential expression and cooperative interaction of c-Ha-ras and c-erbB genes in in vivo chemical carcinogenesis. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[35]  John J. Salley,et al.  Histologic Changes in the Hamster Cheek Pouch During Early Hydrocarbon Carcinogenesis , 1957, Journal of dental research.

[36]  V. Steele,et al.  Prevention of mouse lung tumors by budesonide and its modulation of biomarkers. , 2002, Carcinogenesis.

[37]  C. Cordon-Cardo,et al.  Relation between human papillomavirus positivity and p16 expression in head and neck carcinomas--a tissue microarray study. , 2007, Anticancer research.

[38]  T. Slaga,et al.  Changes in keratin expression during 7,12-dimethylbenz[a]anthracene-induced hamster cheek pouch carcinogenesis. , 1990, Cancer research.

[39]  S. Lippman,et al.  Chemoprevention of aerodigestive epithelial cancers. , 1992, Advances in experimental medicine and biology.

[40]  W. Frankel,et al.  Effects of Lyophilized Black Raspberries on Azoxymethane-Induced Colon Cancer and 8-Hydroxy-2′-Deoxyguanosine Levels in the Fischer 344 Rat , 2001, Nutrition and cancer.

[41]  John D. Potter,et al.  Food, nutrition and the prevention of cancer : a global perspective , 2001 .

[42]  D. Wong,et al.  Expression of c-erbB proto-oncogene during dimethylbenzanthracene-induced tumorigenesis in hamster cheek pouch. , 1987, Oncogene.

[43]  A. Törrönen,et al.  Identification and quantification of phenolic compounds in berries of Fragaria and Rubus species (family Rosaceae). , 2004, Journal of agricultural and food chemistry.

[44]  H. Morgenstern,et al.  Marijuana use and increased risk of squamous cell carcinoma of the head and neck. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[45]  S. Lele,et al.  Overexpression of p16INK4 is a reliable marker of human papillomavirus-induced oral high-grade squamous dysplasia. , 2006, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[46]  K. Chang,et al.  p53 and Ha-ras mutations in chemically induced hamster buccal pouch carcinomas. , 1996, Carcinogenesis.

[47]  Flavonoids potentiate the efficacy of cytarabine through modulation of drug-induced apoptosis. , 2007, Neoplasma.

[48]  M. Pfaffl,et al.  A new mathematical model for relative quantification in real-time RT-PCR. , 2001, Nucleic acids research.

[49]  B. Casto,et al.  Tumor suppressor p16INK4A/Cdkn2a alterations in 7, 12‐dimethylbenz(a)anthracene (DMBA)‐induced hamster cheek pouch tumors , 2008, Molecular carcinogenesis.

[50]  D. Solt,et al.  Anticarcinogenic action of diallyl sulfide in hamster buccal pouch and forestomach. , 1992, Cancer letters.

[51]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[52]  B. Casto,et al.  Chemoprevention of oral cancer by black raspberries. , 2002, Anticancer research.

[53]  G. Stoner,et al.  Randomized Phase II Trial of Lyophilized Strawberries in Patients with Dysplastic Precancerous Lesions of the Esophagus , 2011, Cancer Prevention Research.

[54]  M. Wierzbicka,et al.  Epstein-Barr virus and human papillomavirus infections and oropharyngeal squamous cell carcinomas , 2002, Clinical and Experimental Medicine.

[55]  S. Nagini,et al.  Of humans and hamsters: a comparative evaluation of carcinogen activation, DNA damage, cell proliferation, apoptosis, invasion, and angiogenesis in oral cancer patients and hamster buccal pouch carcinomas. , 2009, Oral oncology.

[56]  V. Steele,et al.  CHEMOPREVENTION OF VINYL CARBAMATE-INDUCED LUNG TUMORS IN STRAIN A MICE , 2000, Experimental lung research.

[57]  Takuji Tanaka,et al.  Chemoprevention of oral carcinogenesis. , 1995, European journal of cancer. Part B, Oral oncology.

[58]  I. Angelillo,et al.  Association between fruit and vegetable consumption and oral cancer: a meta-analysis of observational studies. , 2006, The American journal of clinical nutrition.

[59]  R. Rowe.  Mouth Cancer Foundation , 2012 .

[60]  G. Stoner,et al.  Inhibition of N-nitrosomethylbenzylamine-induced tumorigenesis in the rat esophagus by dietary freeze-dried strawberries. , 2001, Carcinogenesis.

[61]  G. Shklar.  Experimental oral pathology in the Syrian hamster. , 1972, Progress in experimental tumor research.

[62]  Feng Chen,et al.  Statistical analysis of real-time PCR data , 2006, BMC Bioinformatics.

[63]  T. Slaga,et al.  The hamster cheek pouch carcinogenesis model , 1993, Acta odontologica latinoamericana : AOL.

[64]  Honglin Li,et al.  [6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase. , 2009, Cancer research.