Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of a dual inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 tyrosine kinases
- PMID: 17936675
- PMCID: PMC2546572
- DOI: 10.1016/j.oraloncology.2007.08.006
Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of a dual inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 tyrosine kinases
Abstract
Oral cancer is a common neoplasm worldwide with tobacco and alcohol being the major etiological factors contributing to its pathogenesis. Epidermal growth factor receptor (EGFR) and ErbB2 are known to be involved in the development of oral cancer with the former up-regulated in up to 90% human cases. The goal of this study was to evaluate the chemopreventive effects of a dual inhibitor of EGFR and ErbB2 tyrosine kinases, GW2974, in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster cheek pouch model. A short-term experiment (3-week topical DMBA followed by 1-week topical GW2974) was conducted to examine the effects of GW2974 on aberrant arachidonic acid (AA) metabolism and cell proliferation in the hamster oral epithelium. Topical application of 0.1 ml GW2974 (160 microM, three times a week) significantly reduced the levels of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), 5-, 12-, 15-hydroxyeicosatetraenoic acid (HETE), and cell proliferation (BrdU-labeling index). In a long-term post-initiation experiment (6-week topical DMBA followed by 18-week topical GW2974), GW2974 (4 mM and 8 mM) significantly inhibited the incidence, number and size of visible tumors. Under microscope, the numbers of oral lesions (hyperplasia, dysplasia, carcinoma) and the incidence of squamous cell carcinoma (SCC) were also significantly suppressed by GW2974. In summary, our study indicated that dual inhibition of EGFR and ErbB2 tyrosine kinases by GW2974 was effective in preventing oral carcinogenesis in DMBA-induced hamster cheek pouch model. GW2974 exerted its chemopreventive effects in part by suppressing aberrant AA metabolism.
Figures
Similar articles
-
Involvement of the 5-lipoxygenase/leukotriene A4 hydrolase pathway in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch, and inhibition of carcinogenesis by its inhibitors.Carcinogenesis. 2006 Sep;27(9):1902-8. doi: 10.1093/carcin/bgl039. Epub 2006 Apr 21. Carcinogenesis. 2006. PMID: 16632477
-
[Inhibiting effects of GW2974 on DMBA-induced hamster buccal pouch carcinogenesis].Zhonghua Kou Qiang Yi Xue Za Zhi. 2007 Jul;42(7):432-5. Zhonghua Kou Qiang Yi Xue Za Zhi. 2007. PMID: 17961367 Chinese.
-
Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster cheek pouch carcinogenesis by a 5-lipoxygenase inhibitor, garcinol.Nutr Cancer. 2012;64(8):1211-1218. doi: 10.1080/01635581.2012.718032. Epub 2012 Nov 8. Nutr Cancer. 2012. PMID: 23137051 Free PMC article.
-
Zyflamend reduces LTB4 formation and prevents oral carcinogenesis in a 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced hamster cheek pouch model.Carcinogenesis. 2008 Nov;29(11):2182-9. doi: 10.1093/carcin/bgn181. Epub 2008 Aug 6. Carcinogenesis. 2008. PMID: 18687669 Free PMC article.
-
The hamster cheek pouch carcinogenesis model.Acta Odontol Latinoam. 1993;7(1):3-12. Acta Odontol Latinoam. 1993. PMID: 11885256 Review. No abstract available.
Cited by
-
Areca nut components stimulate ADAM17, IL-1α, PGE2 and 8-isoprostane production in oral keratinocyte: role of reactive oxygen species, EGF and JAK signaling.Oncotarget. 2016 Mar 29;7(13):16879-94. doi: 10.18632/oncotarget.7621. Oncotarget. 2016. PMID: 26919242 Free PMC article.
-
GW-2974 and SCH-442416 modulators of tyrosine kinase and adenosine receptors can also stabilize human telomeric G-quadruplex DNA.PLoS One. 2022 Dec 7;17(12):e0277963. doi: 10.1371/journal.pone.0277963. eCollection 2022. PLoS One. 2022. PMID: 36476719 Free PMC article.
-
Inhibitory Effects of Glucosylceramide on Tumorigenesis Induced by a Carcinogen in Mice.Laryngoscope. 2020 Nov;130(11):E593-E597. doi: 10.1002/lary.28449. Epub 2019 Dec 6. Laryngoscope. 2020. PMID: 31808958 Free PMC article.
-
The immunomodulatory impact of naturally derived neem leaf glycoprotein on the initiation progression model of 4NQO induced murine oral carcinogenesis: a preclinical study.Front Immunol. 2024 Mar 22;15:1325161. doi: 10.3389/fimmu.2024.1325161. eCollection 2024. Front Immunol. 2024. PMID: 38585261 Free PMC article.
-
Increased growth inhibitory effects on human cancer cells and anti-inflammatory potency of shogaols from Zingiber officinale relative to gingerols.J Agric Food Chem. 2009 Nov 25;57(22):10645-50. doi: 10.1021/jf9027443. J Agric Food Chem. 2009. PMID: 19877681 Free PMC article.
References
-
- Magrath I, Litvak J. Cancer in developing countries: opportunity and challenge. J Natl Cancer Inst. 1993;85:862–874. - PubMed
-
- Jemal A, Siegel R, Ward E, et al. Cancer Statistics, 2007. CA Cancer J Clin. 2007;57:43–66. - PubMed
-
- Funk GF, Karnell LH, Robinson RA, et al. Presentation, treatment, and outcome of oral cavity cancer: a National Cancer Data Base report. Head Neck. 2002;24:165–180. - PubMed
-
- Sebastian S, Settleman J, Reshkin SJ, et al. The complexity of targeting EGFR signalling in cancer: from expression to turnover. Biochim Biophys Acta. 2006;1766:120–139. - PubMed
-
- Grandis JR, Sok JC. Signaling through the epidermal growth factor receptor during the development of malignancy. Pharmacol Ther. 2004;102:37–46. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous