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Prevention of oral carcinogenesis in rats by Dracaena cinnabari resin extracts

  • Nashwan Al-Afifi
  • Aied Alabsi
  • Fahmi Kaid
  • Marina Bakri
  • Anand Ramanathan
Original Article

Abstract

Objectives

In vivo study was performed to determine the chemopreventive efficacy of the DC resin methanol extract on a 4-nitroquinoline-1-oxide (4NQO) oral cancer animal model.

Materials and methods

This study involves administration of 4NQO solution for 8 weeks alone (cancer induction) or with Dracaena cinnabari (DC) extract at 100, 500, and 1000 mg/kg. DC extract administration started 1 week before exposure until 1 week after the carcinogen exposure was stopped. All rats were sacrificed after 22 weeks, and histological analysis was performed to assess any incidence of pathological changes. Immunohistochemical expressions of selected tumor marker antibodies were analyzed using an image analyzer computer system, and the expression of selected genes involved in apoptosis and proliferative mechanism related to oral cancer were evaluated using RT2-PCR.

Results

The incidence of OSCC decreased with the administration of DC extract at 100, 500, and 1000 mg/kg compared to the induced cancer group. The developed tumor was also observed to be smaller when compared to the induced cancer group. The DC 1000 mg/kg group inhibits the expression of Cyclin D1, Ki-67, Bcl-2, and p53 proteins. It was observed that DC 1000 mg/kg induced apoptosis by upregulation of Bax and Casp3 genes and downregulation of Tp53, Bcl-2, Cox-2, Cyclin D1, and EGFR genes when compared to the induced cancer group.

Conclusions

The data indicated that systemic administration of the DC resin methanol extract has anticarcinogenic potency on oral carcinogenesis.

Clinical relevance

Chemoprevention with DC resin methanol extract may significantly reduce morbidity and possibly mortality from OSCC.

Keywords

Dracaena cinnabari Chemoprevention Oral squamous cell carcinoma 4-Nitroquinoline 1-oxide 

Notes

Funding

This study was financially supported by PPP Grant (PG060-2014A), University of Malaya, Malaysia.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The animal study was approved by the Institutional Animal Care and Use Committee (IACUC), Faculty of Medicine, University of Malaya, Malaysia (Ethics No. 2014-02-14/OBBS/R/NAA).

Informed consent

For this type of study, formal consent is not required.

References

  1. 1.
    Stathopoulou A, Roukos V, Petropoulou C, Kotsantis P, Karantzelis N, Nishitani H, Lygerou Z, Taraviras S (2012) Cdt1 is differentially targeted for degradation by anticancer chemotherapeutic drugs. PLoS One 7(3):e34621CrossRefGoogle Scholar
  2. 2.
    Reddy L, Odhav B, Bhoola K (2003) Natural products for cancer prevention: a global perspective. Pharmacol Ther 99(1):1–13CrossRefGoogle Scholar
  3. 3.
    Tang X-H, Osei-Sarfo K, Urvalek AM, Zhang T, Scognamiglio T, Gudas LJ (2014) Combination of bexarotene and the retinoid CD1530 reduces murine oral-cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide. Proc Natl Acad Sci 111(24):8907–8912CrossRefGoogle Scholar
  4. 4.
    Valente VB, Takamiya AS, Ferreira LL, Felipini RC, Biasoli ÉR, Miyahara GI, Bernabé DG (2016) Oral squamous cell carcinoma misdiagnosed as a denture-related traumatic ulcer: a clinical report. J Prosthet Dent 115(3):259–262CrossRefGoogle Scholar
  5. 5.
    Ragin CC, Taioli E (2007) Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer 121(8):1813–1820CrossRefGoogle Scholar
  6. 6.
    Koh YW, Choi EC, Kang SU, Hwang HS, Lee MH, Pyun J, Park R, Lee Y, Kim C-H (2011) Green tea (−)-epigallocatechin-3-gallate inhibits HGF-induced progression in oral cavity cancer through suppression of HGF/c-Met. J Nutr Biochem 22(11):1074–1083CrossRefGoogle Scholar
  7. 7.
    Bakri M, Cannon R, Holmes A, Rich A (2014) Detection of Candida albicans ADH1 and ADH2 mRNAs in human archival oral biopsy samples. J Oral Pathol Med 43(9):704–710CrossRefGoogle Scholar
  8. 8.
    Bakri M, Rich A, Cannon R, Holmes A (2015) In vitro expression of Candida albicans alcohol dehydrogenase genes involved in acetaldehyde metabolism. Mol Oral Microbiol 30(1):27–38CrossRefGoogle Scholar
  9. 9.
    Saleh A, Kong YH, Vengu N, Badrudeen H, Zain RB, Cheong SC (2014) Dentists’ perception of the role they play in early detection of oral cancer. Asian Pac J Cancer Prev 15(1):229–237CrossRefGoogle Scholar
  10. 10.
    Wali RK, Kunte DP, De La Cruz M, Tiwari AK, Brasky J, Weber CR, Gibson TP, Patel A, Savkovic SD, Brockstein BE (2012) Topical polyethylene glycol as a novel chemopreventive agent for oral cancer via targeting of epidermal growth factor response. PLoS One 7(6):e38047CrossRefGoogle Scholar
  11. 11.
    Carelle N, Piotto E, Bellanger A, Germanaud J, Thuillier A, Khayat D (2002) Changing patient perceptions of the side effects of cancer chemotherapy. Cancer 95(1):155–163CrossRefGoogle Scholar
  12. 12.
    Gottesman MM (2002) Mechanisms of cancer drug resistance. Annu Rev Med 53(1):615–627CrossRefGoogle Scholar
  13. 13.
    Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, (eds) CK (2016) SEER cancer statistics review, 1975–2013, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2013/, based on November 2015 SEER data submission, posted to the SEER web site, April 2016
  14. 14.
    McCormick DL, Horn TL, Johnson WD, Peng X, Lubet RA, Steele VE (2015) Suppression of rat oral carcinogenesis by agonists of peroxisome proliferator activated receptor γ. PLoS One 10(10):e0141849CrossRefGoogle Scholar
  15. 15.
    Sporn MB (1976) Approaches to prevention of epithelial cancer during the preneoplastic period. Cancer Res 36(7 Part 2):2699–2702PubMedGoogle Scholar
  16. 16.
    Tanaka T, Tanaka M, Tanaka T (2011) Oral carcinogenesis and oral cancer chemoprevention: a review. Pathol Res Int 2011:1–10.  https://doi.org/10.4061/2011/431246 CrossRefGoogle Scholar
  17. 17.
    Schwartz JL (2000) Biomarkers and molecular epidemiology and chemoprevention of oral carcinogenesis. Crit Rev Oral Biol Med 11(1):92–122CrossRefGoogle Scholar
  18. 18.
    Soria J-C, Kim ES, Fayette J, Lantuejoul S, Deutsch E, Hong WK (2003) Chemoprevention of lung cancer. The lancet oncology 4(11):659–669CrossRefGoogle Scholar
  19. 19.
    Shukla Y, Pal SK (2004) Dietary cancer chemoprevention: an overview. Int J Hum Genet 4(4):265–276CrossRefGoogle Scholar
  20. 20.
    Hubálková I, Maděra P, Volařík D (2015) Growth dynamics of Dracaena cinnabari under controlled conditions as the most effective way to protect endangered species. Saudi J Biol Sci 24(7):1445–1452.  https://doi.org/10.1016/j.sjbs.2015.09.011 CrossRefGoogle Scholar
  21. 21.
    Gupta D, Bleakley B, Gupta RK (2008) Dragon’s blood: botany, chemistry and therapeutic uses. J Ethnopharmacol 115(3):361–380.  https://doi.org/10.1016/j.jep.2007.10.018 CrossRefPubMedGoogle Scholar
  22. 22.
    Alexander D, Miller A (1996) Saving the spectacular flora of Socotra. Plant Talk 7:19–22Google Scholar
  23. 23.
    Mothana R, Gruenert R, Lindequist U, Bednarski P (2007) Study of the anticancer potential of Yemeni plants used in folk medicine. Die Pharmazie-An International Journal of Pharmaceutical Sciences 62(4):305–307Google Scholar
  24. 24.
    Yehia A-TA, Alzowahi FAM, Kadam TA, Shaikh RU (2013) In vitro evaluation of antimicrobial and antioxidant activity of Dragon’s blood tree (Dracaena cinnabari Balf. f.) of Socotra Island (Yemen). J Coast Life Med 1(2):123–129Google Scholar
  25. 25.
    Gupta D, Bleakley B, Gupta RK (2009) Bioassay guided isolation of antibacterial homoisoflavone from Dragon’s blood resin (Dammul-akhwain). Natural Product Radiance 8(5):494–497Google Scholar
  26. 26.
    Mothana RA, Lindequist U (2005) Antimicrobial activity of some medicinal plants of the island Soqotra. J Ethnopharmacol 96(1):177–181CrossRefGoogle Scholar
  27. 27.
    Gupta D, Verma N, Das HR, Gupta RK (2014) Evaluation of anti-inflammatory activity of Dracaena cinnabari Balf. f. resin. Indian J Nat Prod Resour 5(3):215–222Google Scholar
  28. 28.
    Alabsi AM, Li LK, Paterson IC, Ali-Saeed R, Moharam BA (2016) Cell cycle arrest and apoptosis induction via modulation of mitochondrial integrity by Bcl-2 family members and caspase-dependent in dracaena cinnabari-treated H400 human oral squamous cell carcinoma. Biomed Res Int 2016:1–13CrossRefGoogle Scholar
  29. 29.
    Al-Afifi NA, Alabsi AM, Bakri MM, Ramanathan A (2018) Acute and sub-acute oral toxicity of Dracaena cinnabari resin methanol extract in rats. BMC Complement Altern Med 18(1):50CrossRefGoogle Scholar
  30. 30.
    Tanaka T, Ishigamori R (2011) Understanding carcinogenesis for fighting oral cancer. J Oncol 2011:1–10Google Scholar
  31. 31.
    Zhang M, Wang F, Jiang L, Liu R, Zhang L, Lei X, Li J, Jiang J, Guo H, Fang B (2013) Lactobacillus salivarius REN inhibits rat oral cancer induced by 4-nitroquioline 1-oxide. Cancer Prev Res 6(7):686–694CrossRefGoogle Scholar
  32. 32.
    Tanaka T, Kawabata K, Kakumoto M, Matsunaga K, Mori H, Murakami A, Kuki W, Takahashi Y, Yonei H, Satoh K (1998) Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by citrus auraptene in rats. Carcinogenesis 19(3):425–431CrossRefGoogle Scholar
  33. 33.
    Barcessat ARR, Huang I, Rabelo GD, Rosin FCP, Ferreira LGV, Cerqueira Luz JG, Corrêa L (2014) Systemic toxic effects during early phases of topical 4-NQO-induced oral carcinogenesis in rats. J Oral Pathol Med 43(10):770–777CrossRefGoogle Scholar
  34. 34.
    Tomayko MM, Reynolds CP (1989) Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol 24(3):148–154CrossRefGoogle Scholar
  35. 35.
    Ribeiro DA, Kitakawa D, Domingues MAC, Cabral LAG, Marques MEA, Salvadori DMF (2007) Survivin and inducible nitric oxide synthase production during 4NQO-induced rat tongue carcinogenesis: a possible relationship. Exp Mol Pathol 83(1):131–137CrossRefGoogle Scholar
  36. 36.
    El-Rouby DH (2011) Histological and immunohistochemical evaluation of the chemopreventive role of lycopene in tongue carcinogenesis induced by 4-nitroquinoline-1-oxide. Arch Oral Biol 56(7):664–671CrossRefGoogle Scholar
  37. 37.
    Shu J, Dolman G, Duan J, Qiu G, Ilyas M (2016) Statistical colour models: an automated digital image analysis method for quantification of histological biomarkers. Biomed Eng Online 15(1):46.  https://doi.org/10.1186/s12938-016-0161-6 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Katsha A, Wang L, Arras J, Omar OM, Ecsedy JA, Belkhiri A, El-Rifai W (2017) Activation of EIF4E by Aurora kinase A depicts a novel druggable axis in everolimus resistant cancer cells. Clin Cancer Res 23(14):3756–3768CrossRefGoogle Scholar
  39. 39.
    Lee U-L, Choi S-W (2011) The chemopreventive properties and therapeutic modulation of green tea polyphenols in oral squamous cell carcinoma. ISRN Oncol 2011:1–7.  https://doi.org/10.5402/2011/403707 CrossRefGoogle Scholar
  40. 40.
    Patel BM, Damle D (2013) Combination of telmisartan with cisplatin controls oral cancer cachexia in rats. Biomed Res Int 2013:1–10CrossRefGoogle Scholar
  41. 41.
    Hasina R, Martin LE, Kasza K, Jones CL, Jalil A, Lingen MW (2009) ABT-510 is an effective chemopreventive agent in the mouse 4-nitroquinoline 1-oxide model of oral carcinogenesis. Cancer Prev Res 2(4):385–393CrossRefGoogle Scholar
  42. 42.
    Yoshida K, Tanaka T, Hirose Y, Yamaguchi F, Kohno H, Toida M, Hara A, Sugie S, Shibata T, Mori H (2005) Dietary garcinol inhibits 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in rats. Cancer Lett 221(1):29–39CrossRefGoogle Scholar
  43. 43.
    Takeuchi S, Nakanishi H, Yoshida K, Yamamoto S, Tonoki H, Tsukamoto T, Fukushima S, Moriuchi T, Kurita K, Tatematsu M (2000) Isolation of differentiated squamous and undifferentiated spindle carcinoma cell lines with differing metastatic potential from a 4-nitroquinoline N-oxide-induced tongue carcinoma in a F344 rat. Jpn J Cancer Res 91(12):1211–1221CrossRefGoogle Scholar
  44. 44.
    Kanojia D, Vaidya MM (2006) 4-Nitroquinoline-1-oxide induced experimental oral carcinogenesis. Oral Oncol 42(7):655–667CrossRefGoogle Scholar
  45. 45.
    Tang X-H, Knudsen B, Bemis D, Tickoo S, Gudas LJ (2004) Oral cavity and esophageal carcinogenesis modeled in carcinogen-treated mice. Clin Cancer Res 10(1):301–313CrossRefGoogle Scholar
  46. 46.
    Fearon K, Preston T (1990) Body composition in cancer cachexia. Transfus Med Hemother 17(Suppl. 3):63–66CrossRefGoogle Scholar
  47. 47.
    Thandavamoorthy P, Balan R, Subramaniyan J, Arumugam M, John B, Krishnan G, Ramasamy E, Mani GK, Rajendran R, Thiruvengadam D (2014) Alleviative role of rutin against 4-nitroquinoline-1-oxide (4-NQO) provoked oral squamous cell carcinoma in experimental animal model. J Pharm Res 8(7):899–906Google Scholar
  48. 48.
    Droguett D, Castillo C, Leiva E, Theoduloz C, Schmeda-Hirschmann G, Kemmerling U (2015) Efficacy of quercetin against chemically induced murine oral squamous cell carcinoma. Oncol Lett 10(4):2432–2438CrossRefGoogle Scholar
  49. 49.
    Ribeiro DA, Salvadori DMF, da Silva RN, Darros BR, Marques MEA (2004) Genomic instability in non-neoplastic oral mucosa cells can predict risk during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. Oral Oncol 40(9):910–915CrossRefGoogle Scholar
  50. 50.
    Zhao J, Wang Z, Han J, Qiu X, Pan J, Chen J (2014) Increased frequency of CD4+ CD25+ FOXP3+ cells correlates with the progression of 4-nitroquinoline1-oxide-induced rat tongue carcinogenesis. Clin Oral Investig 18(7):1725–1730CrossRefGoogle Scholar
  51. 51.
    Yamamoto K, Kitayama W, Denda A, Morisaki A, Kuniyasu H, Inoue M, Kirita T (2004) Suppressive effects of a selective cyclooxygenase-2 inhibitor, etodolac, on 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. Exp Toxicol Pathol 56(3):145–151CrossRefGoogle Scholar
  52. 52.
    Peng X, Li W, Johnson WD, Torres KE, McCormick DL (2015) Overexpression of lipocalins and pro-inflammatory chemokines and altered methylation of PTGS2 and APC2 in oral squamous cell carcinomas induced in rats by 4-nitroquinoline-1-oxide. PLoS One 10(1):e0116285CrossRefGoogle Scholar
  53. 53.
    Huang S-F, Cheng S-D, Chuang W-Y, Chen I-H, Liao C-T, Wang H-M, Hsieh L-L (2012) Cyclin D1 overexpression and poor clinical outcomes in Taiwanese oral cavity squamous cell carcinoma. World J Surg Oncol 10(1):40–47CrossRefGoogle Scholar
  54. 54.
    Shan J, Zhao W, Gu W (2009) Suppression of cancer cell growth by promoting cyclin D1 degradation. Mol Cell 36(3):469–476CrossRefGoogle Scholar
  55. 55.
    Kaminagakura E, Werneck da Cunha I, Soares FA, Nishimoto IN, Kowalski LP (2011) CCND1 amplification and protein overexpression in oral squamous cell carcinoma of young patients. Head Neck 33(10):1413–1419CrossRefGoogle Scholar
  56. 56.
    Michalides R, van Veelen N, Hart A, Loftus B, Wientjens E, Balm A (1995) Overexpression of cyclin D1 correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck. Cancer Res 55 (5):975–978Google Scholar
  57. 57.
    Saawarn S, Astekar M, Saawarn N, Dhakar N, Gomateshwar Sagari S (2012) Cyclin d1 expression and its correlation with histopathological differentiation in oral squamous cell carcinoma. Sci World J 2012:1–5.  https://doi.org/10.1100/2012/978327 CrossRefGoogle Scholar
  58. 58.
    Perez-Ordonez B, Beauchemin M, Jordan R (2006) Molecular biology of squamous cell carcinoma of the head and neck. J Clin Pathol 59(5):445–453CrossRefGoogle Scholar
  59. 59.
    Yoshida K, Hirose Y, Tanaka T, Yamada Y, Kuno T, Kohno H, Katayama M, Qiao Z, Sakata K, Sugie S (2003) Inhibitory effects of troglitazone, a peroxisome proliferator-activated receptor γ ligand, in rat tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide. Cancer Sci 94(4):365–371CrossRefGoogle Scholar
  60. 60.
    Tumuluri V, Thomas G, Fraser I (2002) Analysis of the Ki-67 antigen at the invasive tumour front of human oral squamous cell carcinoma. J Oral Pathol Med 31(10):598–604CrossRefGoogle Scholar
  61. 61.
    Cotter TG (2009) Apoptosis and cancer: the genesis of a research field. Nat Rev Cancer 9(7):501–507CrossRefGoogle Scholar
  62. 62.
    Plati J, Bucur O, Khosravi-Far R (2011) Apoptotic cell signaling in cancer progression and therapy. Integr Biol 3(4):279–296CrossRefGoogle Scholar
  63. 63.
    Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9(1):47–59CrossRefGoogle Scholar
  64. 64.
    Kang N, Zhang J-H, Qiu F, S-i T, Onodera S, Ikejima T (2010) Inhibition of EGFR signaling augments oridonin-induced apoptosis in human laryngeal cancer cells via enhancing oxidative stress coincident with activation of both the intrinsic and extrinsic apoptotic pathways. Cancer Lett 294(2):147–158CrossRefGoogle Scholar
  65. 65.
    Wang J, Jia L, Kuang Z, Wu T, Hong Y, Chen X, Leung WK, Xia J, Cheng B (2014) The in vitro and in vivo antitumor effects of clotrimazole on oral squamous cell carcinoma. PLoS One 9(6):e98885CrossRefGoogle Scholar
  66. 66.
    Choi J, Chung S, Lee G, Kim B, Kim J, Kook E, Jang M, Ko M, Jung K, Choi R, Kim O (2005) Expression of Bcl-2 family in 4-nitroquinoline 1-oxide-induced tongue carcinogenesis of the rat. J Oral Med Pain 30(3):301–317Google Scholar
  67. 67.
    Tait SW, Green DR (2013) Mitochondrial regulation of cell death. Cold Spring Harb Perspect Biol 5(9):a008706CrossRefGoogle Scholar
  68. 68.
    Xie X, Clausen OPF, Angelis PD, Boysen M (1999) The prognostic value of spontaneous apoptosis, Bax, Bcl-2, and p53 in oral squamous cell carcinoma of the tongue. Cancer 86(6):913–920CrossRefGoogle Scholar
  69. 69.
    Ravi D, Nalinakumari K, Rajaram R, Nair MK, Pillai MR (1996) Expression of programmed cell death regulatory p53 and bcl-2 proteins in oral lesions. Cancer Lett 105(2):139–146CrossRefGoogle Scholar
  70. 70.
    Kaur J, Srivastava A, Ralhan R (1994) Overexpression of p53 protein in betel-and tobacco-related human oral dysplasia and squamous-cell carcinoma in India. Int J Cancer 58(3):340–345CrossRefGoogle Scholar
  71. 71.
    Chin D, Boyle GM, Theile DR, Parsons PG, Coman WB (2004) Molecular introduction to head and neck cancer (HNSCC) carcinogenesis. Br J Plast Surg 57(7):595–602CrossRefGoogle Scholar
  72. 72.
    Scrobota I, Bolfa P, Filip A, Catoi C, Alb C, Pop O, Tatomir C, Baciut G (2016) Natural chemopreventive alternatives in oral cancer chemoprevention. J Physiol Pharmacol 67(1):161–172PubMedGoogle Scholar
  73. 73.
    Patil NN, Wadhwan V, Chaudhary M, Nayyar AS (2016) KAI-1 and p53 expression in oral squamous cell carcinomas: markers of significance in future diagnostics and possibly therapeutics. J Oral Maxillofac Pathol 20(3):384–389CrossRefGoogle Scholar
  74. 74.
    Mercer W (1992) Cell cycle regulation and the p53 tumor suppressor protein. Crit Rev Eukaryot Gene Expr 2(3):251–263PubMedGoogle Scholar
  75. 75.
    Rivlin N, Brosh R, Oren M, Rotter V (2011) Mutations in the p53 tumor suppressor gene important milestones at the various steps of tumorigenesis. Genes Cancer 2(4):466–474CrossRefGoogle Scholar
  76. 76.
    Osugi Y (1996) p53 expression in various stages of 4-nitroquinoline 1-oxide induced carcinoma in the rat tongue. J Osaka Dent Univ 30(1_2):29–35PubMedGoogle Scholar
  77. 77.
    Strano S, Dell'Orso S, Di Agostino S, Fontemaggi G, Sacchi A, Blandino G (2007) Mutant p53: an oncogenic transcription factor. Oncogene 26(15):2212–2219CrossRefGoogle Scholar
  78. 78.
    Maltzman W, Czyzyk L (1984) UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells. Mol Cell Biol 4(9):1689–1694CrossRefGoogle Scholar
  79. 79.
    Fong LY, Jiang Y, Rawahneh ML, Smalley KJ, Croce CM, Farber JL, Huebner K (2011) Zinc supplementation suppresses 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis. Carcinogenesis 32(4):554–560CrossRefGoogle Scholar
  80. 80.
    Wang Z (2005) The role of COX-2 in oral cancer development, and chemoprevention/treatment of oral cancer by selective COX-2 inhibitors. Curr Pharm Des 11(14):1771–1777CrossRefGoogle Scholar
  81. 81.
    Ribeiro DA, Fracalossi ACC, Gomes TS, Oshima CT (2009) COX-2 expression during 4-nitroquinoline 1-oxide induced rat tongue carcinogenesis. Basic Appl Pathol 2(1):9–14CrossRefGoogle Scholar
  82. 82.
    McCormick DL, Phillips JM, Horn TL, Johnson WD, Steele VE, Lubet RA (2010) Overexpression of cyclooxygenase-2 in rat oral cancers and prevention of oral carcinogenesis in rats by selective and nonselective COX inhibitors. Cancer Prev Res 3(1):73–81CrossRefGoogle Scholar
  83. 83.
    Ribeiro d MC, Gollucke A, Ferreira M, Catharino R, Aguiar O, Spadari R, Barbisan L, Ribeiro D (2014) Chemopreventive activity of apple extract following medium-term oral carcinogenesis assay induced by 4-nitroquinoline-1-oxide. Arch Oral Biol 59(8):815–821CrossRefGoogle Scholar
  84. 84.
    Benchekroun MT, Saintigny P, Thomas SM, El-Naggar AK, Papadimitrakopoulou V, Ren H, Lang W, Fan Y-H, Huang J, Feng L (2010) Epidermal growth factor receptor expression and gene copy number in the risk of oral cancer. Cancer Prev Res 3(7):800–809CrossRefGoogle Scholar
  85. 85.
    Khan N, Afaq F, Saleem M, Ahmad N, Mukhtar H (2006) Targeting multiple signaling pathways by green tea polyphenol (−)-epigallocatechin-3-gallate. Cancer Res 66(5):2500–2505CrossRefGoogle Scholar
  86. 86.
    Singh BN, Shankar S, Srivastava RK (2011) Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem Pharmacol 82(12):1807–1821CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Nashwan Al-Afifi
    • 1
  • Aied Alabsi
    • 1
    • 2
  • Fahmi Kaid
    • 1
  • Marina Bakri
    • 1
  • Anand Ramanathan
    • 3
    • 4
  1. 1.Department of Oral and Craniofacial Sciences, Faculty of DentistryUniversity of MalayaKuala LumpurMalaysia
  2. 2.Department of Oral Biology and Biomedical Sciences, Faculty of DentistryMAHSA UniversityJenjaromMalaysia
  3. 3.Department of Oral & Maxillofacial Clinical Sciences, Faculty of DentistryUniversity of MalayaKuala LumpurMalaysia
  4. 4.Oral Cancer Research and Coordinating Centre, Faculty of DentistryUniversity of MalayaKuala LumpurMalaysia

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