The role of matrix metalloproteinases 2 and 9 during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide

Fracalossi, Ana Carolina Cuzzuol; Miranda, Sandra Regina; Oshima, Celina T. F.; Franco, Marcello; Ribeiro, Daniel Araki

doi:10.1007/s10735-010-9258-6

Cited by 18 publications

(12 citation statements)

References 29 publications

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“…Increased expression levels of MMP-9 have been observed in oral precancerous lesions as well as in oral cancer (23). The increased expression may be associated with the transformation of oral precancerous lesions to oral cancer (24,25) and in oral carcinogenesis (11). A previous in vitro study revealed that TNF-α stimulated the production of MMP-9 in a precancerous keratinocyte cell line (26).…”

Section: Discussionmentioning

confidence: 98%

Upregulated expression of MMP-9 in gingival epithelial cells induced by prolonged stimulation with arecoline

et al. 2017

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Abstract. Betel quid chewing is implicated in the high prevalence of oral cancer in Southeast Asian countries. One of the major components of betel quid is arecoline. In the present study, in order to characterize the association between chronic arecoline stimulation and carcinogenesis the expression level of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 mRNA in human gingival epithelial progenitor cells (HGEPs) stimulated with arecoline was assessed. The HGEPs were alternated between 3 days of incubation with arecoline (50 µg/ml), and 3 days without arecoline, for up to 30 days. The expression levels of the MMPs and TIMPs in the cells stimulated with arecoline were evaluated by reverse transcription-quantitative polymerase chain reaction at 18 and 30 days. The expression of MMP-9 mRNA in the experimental group was significantly increased compared with in the control group (P<0.01). No significant differences in the expression of MMP-2, TIMP-1 or TIMP-2 mRNA were observed between the experimental and control groups. Using an MMP-9 activity assay, the levels of MMP-9 activity in the experimental group were demonstrated to be significantly higher than in the control group (P<0.05). To investigate associated cellular signaling pathways, PDTC [a nuclear factor (NF)-κB/inhibitor of NF-κB (IκB) inhibitor], PD98059 [a mitogen-activated protein kinase kinase (MAPKK)1 and MAPKK2 inhibitor], SB203580 (a p38 MAPK inhibitor) and 5,15-DPP [a signal transduction and activator of transcription (STAT) 3 inhibitor] were used. All inhibitors decreased the extent of MMP-9 upregulation induced by stimulation with arecoline. Based on the data, it is hypothesized that MMP-9 activity may be involved in the pathological alterations of oral epithelium induced by betel quid chewing, and that the NF-κB/IκB, MAPK, p38 MAPK and STAT3 signaling pathways may be involved in the production of MMP-9 induced by betel quid chewing.

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Section: Discussionmentioning

confidence: 98%

Upregulated expression of MMP-9 in gingival epithelial cells induced by prolonged stimulation with arecoline

et al. 2017

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“…A well-known way to establish an animal experimental model to study oral carcinogenesis is by the administration of the water-soluble compound 4-nitroquinoline 1-oxide (4-NQO) (Ribeiro et al 2007;Fracalossi et al 2010;Carvalho et al 2012). The medium-term assay is based on the multi-step process of carcinogenesis characterized by initiation, promotion and tumor progression.…”

Section: W Limmentioning

confidence: 99%

“…They were maintained under controlled conditions of temperature (24 ± 2°C), light-dark periods of 12 h, and with free access to water and commercial diet (Damul Science). The animals were treated for 6 months with 50 ppm 4-NQO (Sigma-Aldrich, St. Louis, USA) solution supplied in the drinking water (Fracalossi et al 2010;Miranda et al 2011). All rats were allowed access to the drinking water, which was replaced twice a week with freshly prepared solution.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Expression of cancer stem cell marker during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis

et al. 2014

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One of the theories regarding oral carcinogenesis is that the tumor growth is initiated from cancer stem cells (CSCs) that self-renew and give rise to differentiated tumor cells, like stem cells do in normal tissues. The most common methods of CSC identification are based on CSC marker expression in carcinogenesis. This study examined the expression of CD133 and CD44, the most commonly used CSC biomarkers in oral squamous cell sarcoma (SCC), with the goal of identifying molecular biomarkers whose expression is associated with the multistep oral carcinogenesis. The expression of CD133, CD44, proliferating cell nuclear antigen (PCNA), and Cytokeratin (CK) was examined by Western blot analysis and confirmed by immunohistochemistry in a 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis model. Also, the expression of aldehyde dehydrogenase 1 (ALDH1), OCT-4 and Nanog were investigated for alteration of cancer cell stemness by Western blot. Along with the progress of multistep carcinogenesis, there were slight increases of CD133 and CD44 expression in the dysplasia group compared with normal rats. However, CD133 protein level was significantly overexpressed in SCC. The expression of PCNA and CK were low in normal group, but sequentially increased in SCC. ALDH1, Nanog and OCT-4 expression were significantly increased according to SCC grade during carcinogenesis. The findings indicate that CD133 is useful in identifying oral CSCs, which suggests that CD133 may serve as a predictor to identify CSCs with a high risk of oral cancer development.

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“…They were maintained under controlled conditions of temperature (24 ± 2°C), light-dark periods of 12 h, and with free access to water and commercial diet (Nuvital PR, Brazil). The animals were distributed into 3 groups of 10 rats each and were treated with 50 ppm 4NQO (Sigma Aldrich, St. Louis, USA) solution by drinking water for 4, 12 or 20 weeks as previously established (Miranda et al 2011;Fracalossi et al 2010). Ten animals were used as negative control and were sacrificed at the beginning the experiment (zero week).…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Alkylation-induced genotoxicity as a predictor of DNA repair deficiency following experimental oral carcinogenesis

et al. 2012

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The aim of this study was to evaluate alkylation induced genotoxicity as a result of DNA repair deficiency during 4-nitroquinoline 1-oxide (4NQO)-induced rat tonguecarcinogenesis by means of single cell gel (comet)assay. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12, and 20 weeks.Ten animals were used as negative control. Blood samples and oral mucosa cells collected from all animals were divided into two aliquots of 20 lL each to study basal DNA damage and DNA damage due to genotoxin sensitivity.The first aliquot was processed immediately for comet assay to assess basal DNA damage. The second aliquot was treated with a known genotoxin, methylmetanesulfonate.Significantly greater DNA damage was noticed to oral mucosa cells from 4, and 12 weeks posttreatment.Peripheral blood cells did show statistically significant differences (P\0.05) after 20 weeks-group(squamous cell carcinoma). In conclusion, alkylation induced genotoxicity as a result of DNA repair deficiency is present in oral mucosa cells following oral experimental carcinogenesis.

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The role of matrix metalloproteinases 2 and 9 during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide

Cited by 18 publications

References 29 publications

Upregulated expression of MMP-9 in gingival epithelial cells induced by prolonged stimulation with arecoline

Upregulated expression of MMP-9 in gingival epithelial cells induced by prolonged stimulation with arecoline

Expression of cancer stem cell marker during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis

Alkylation-induced genotoxicity as a predictor of DNA repair deficiency following experimental oral carcinogenesis

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