Anthracene Induced Hamster Buccal Pouch Research Articles

Chemopreventive Potential of Coumarin in 7,12-dimethylbenz[a] anthracene Induced Hamster Buccal Pouch Carcinogenesis

The aim of the present study was to investigate the chemopreventive effect of coumarin against 7, 12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis by monitoring tumor incidence and histopathological changes as well as by analyzing the status of biochemical markers (lipid peroxidation, enzymatic and non-enzymatic antioxidants, phase I and phase II detoxification enzymes). Oral squamous cell carcinomas were induced in the buccal pouch of Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. We noted 100% tumor formation with marked abnormalities in the biomarkers status in hamsters treated with DMBA alone. Oral administration of coumarin at a dose of 100 mg/kg body weight (bw) to DMBA treated hamsters completely prevented the tumor formation as well as restored the status of biochemical variables. The results of the present study thus suggest that the chemopreventive effect of coumarin is probably due to its anti-lipid peroxidative potential and modulating effect on carcinogen detoxification agents in favor of the excretion of ultimate carcinogenic metabolites of DMBA during DMBA-induced hamster buccal pouch carcinogenesis.

Apigenin prevents deregulation in the expression pattern of cell-proliferative, apoptotic, inflammatory and angiogenic markers during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis

ObjectiveMalignant tumour arises due to abnormal cell proliferation, chronic inflammation, defect in apoptotic pathway and unwanted angiogenesis. The present study has investigated the modulating effect of apigenin on expression pattern of apoptotic (p53, Bcl-2, Bax, Caspase-3 and 9) cell proliferative (PCNA, Cyclin D1, c-fos), angiogenic (VEGF) and inflammatory (NFκB, COX-2) markers during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Materials and methodsOral squamous cell carcinoma was developed in the buccal pouches of golden Syrian hamsters by painting with 0.5% DMBA three times a week for 14 weeks. Deregulation in the expression of the cell proliferation, apoptosis, inflammation and angiogenesis markers was noticed in hamsters treated with DMBA alone. ResultsOral administration of apigenin at a dose of 2.5mg/kgbw prevented the deregulation of the above mentioned molecular markers in hamsters treated with DMBA. ConclusionOur results thus suggest that apigenin exhibited anti-cell proliferative, anti-inflammatory, anti-angiogenic and apoptotic potential during DMBA-induced hamster buccal pouch carcinogenesis.

Geraniol modulates cell proliferation, apoptosis, inflammation, and angiogenesis during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis

Oral carcinogenesis, a multistep process with multifaceted etiology, arises due to accumulation of heterogeneous genetic changes in the genes involved in the basic cellular functions including cell division, differentiation, and cell death. These genetic changes in the affected cell progressively increase the cell proliferation, angiogenesis, and inhibition of apoptosis. The present study investigated the modulating effect of geraniol on the expression pattern of cell proliferative (PCNA, cyclin D1, c-fos), inflammatory (NF-κB, COX-2), apoptotic (p53, Bax, Bcl-2, caspase-3 and -9), and angiogenic (VEGF) markers in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Topical application of 0.5 % DMBA in liquid paraffin, three times a week, for 14 weeks, developed well-differentiated squamous cell carcinoma (SCC) in the buccal pouch of golden Syrian hamsters. All the hamsters treated with DMBA alone (100 %) developed oral tumors in the buccal pouch after 14 weeks. Over-expression of mutant p53, PCNA, Bcl-2, and VEGF accompanied by decreased expression of Bax were noticed in hamsters treated with DMBA alone. Increased expression of c-fos, COX-2, NF-κB, and cyclin D1 and decreased activities of caspase-3 and -9 were also noticed in hamsters treated with DMBA alone. Oral administration of geraniol at a dose of 250 mg/kg bw (body weight) not only completely prevented the formation of oral tumors but also prevented the deregulation in the expression of above mentioned molecular markers in hamsters treated with DMBA. The present results thus suggest that geraniol has potent anti-inflammatory, anti-angiogenic, anti-cell proliferative, and apoptosis-inducing properties in DMBA-induced hamster buccal pouch carcinogenesis.

Successful treatment of 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch precancerous lesions by topical 5-aminolevulinic acid-mediated photodynamic therapy

Our previous studies found that topical 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (ALA-PDT) with a light dose of 100 J/cm(2) is very effective for human oral precancerous lesions. In this study, 20 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch precancerous lesions were treated by topical ALA-PDT with a light dose of either 75 J/cm(2) (n = 10) or 100 J/cm(2) (n = 10) using a 640-nm light-emitting diode (LED) light to test which light dose could achieve a better clinical outcome. The 10 precancerous lesions treated by 75-J ALA-PDT showed complete response in 8 after an average of 3.4 (range, 2-6) treatments and partial response in 2. The 10 precancerous lesions treated by 100-J ALA-PDT demonstrated complete response in 7 after an average of 4.4 (range, 3-6) treatments and partial response in 3. Fisher exact test showed no significant difference in clinical outcome between these two treatment modalities (p = 1.000). One complete-response precancerous lesion in the 75-J ALA-PDT group recurred at the end of 19-week follow-up and another complete response precancerous lesion in the 100-J ALA-PDT group recurred at the end of 16-week follow-up. Both recurrence lesions were treated by the original topical ALA-PDT regimen and demonstrated complete response after 3 PDT treatments. Furthermore, the 5 partial-response precancerous lesions developed into squamous cell carcinomas after 30-week follow-up. Our findings indicate that both the 75-J and 100-J topical ALA-PDT treatment modalities are very effective for DMBA-induced hamster buccal pouch precancerous lesions and no significant difference in clinical outcome between these two treatment modalities.

Pro-apoptotic and anti-inflammatory potential of andrographolide during 7,12-dimethylbenz[a]anthracene induced hamster buccal pouch carcinogenesis

Objective: Aim of the present study was to investigate the modulating effect of andrographolide on apoptotic and inflammatory markers during 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Methods: Oral tumors were developed in the buccal pouch of golden Syrian hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. The expression pattern of molecular markers were assayed using immunohistochemistry (p53, Bcl-2 and Bax), ELISA (COX-2) and real-time PCR (NFκB). Results: We noticed 100% tumor formation accompanied by deregulation in the apoptotic and inflammatory markers in the buccal mucosa of hamsters treated with DMBA alone. Oral administration of andrographolide at a dose of 50 mg/kg b.w to hamsters treated with DMBA, not only completely prevented the tumor formation but also modulated the status of above mentioned molecular markers in favor of inhibiting cell proliferation as evidenced by no tumor formation.

Protective effect of 18β-glycyrrhetinic acid on cell surface glycoconjugates abnormalities in 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis

Aim: The aim of this study was to evaluate the protective effect of 18β-glycyrrhetinic acid against cell surface glycoconjugates (protein-bound hexose, hexosamine, sialic acid, and fucose) abnormalities in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Materials and Methods: Topical application of DMBA three times a week for 14 weeks on the buccal pouches of hamsters resulted in well-developed squamous cell carcinoma. Glycoconjugates status in plasma and tumor tissues were estimated using specific and sensitive colorimetric methods. Results: Increases in plasma and tumor tissue glycoconjugates were noticed in hamsters treated with DMBA. Oral administration of glycyrrhetinic acid at a dose of 45 mg/kg body weight restored the status of glycoconjugates in hamsters treated with DMBA. Conclusion: The results of this study suggest that glycyrrhetinic acid might provide protection against cell surface abnormalities during DMBA-induced buccal pouch carcinogenesis in hamsters.

Protective Effect of Berberine on Expression Pattern of Apoptotic, Cell Proliferative, Inflammatory and Angiogenic Markers During 7,12-dimethylbenz(a)anthracene Induced Hamster Buccal Pouch Carcinogenesis

Investigation of expression pattern of molecular markers in oral epithelial tissues would help to assess the cell differentiation and proliferation as well as early diagnosis of precancerous and cancerous lesions of the oral cavity. Aim of the present study was to investigate the protective effect of berberine on expression pattern of apoptotic, cell proliferative, inflammatory and angiogenic markers during 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Immunohistochemical staining [p53, Bcl-2, Bax, Proliferating Cell Nuclear Antigen (PCNA) and Vascular Endothelial Growth Factor (VEGF)], Enzyme Linked Immuno Sorbent Assay (ELISA) [c-fos, COX-2, caspase-3 and -9] and Real-Time PCR [Cyclin D1 and NFkappaB] were utilized to assess the expression pattern of molecular markers in DMBA induced hamster buccal pouch carcinogenesis. Over expression of mutant p53, PCNA, Bcl-2 and VEGF were noticed in hamsters treated with DMBA alone. Decreased expression of Bax protein was noticed in hamsters treated with DMBA alone. Increased expression of C-fos, COX-2, NFkappaB and Cyclin D1 and decreased activities of caspase-3 and -9 were also noticed in hamsters treated with DMBA alone. Oral administration ofberberine at a dose of 75 mg kg(-1) b.w. brought back the expression of above mentioned molecular markers to near normal pattern in hamsters treated with DMBA. The present results thus suggest that berberine has potent anti-inflammatory, anti-angiogenic, anti-cell proliferative and apoptosis inducing properties in DMBA induced oral carcinogenesis.

Chemopreventive efficacy of geraniol against 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis

The status of lipid peroxidation, antioxidants, and detoxification enzymes were used as biochemical end points to assess the chemopreventive potential of geraniol, a monoterpene, in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Topical application of 0.5% DMBA in liquid paraffin, three times a week, for 14 weeks developed well-differentiated squamous cell carcinoma in the buccal pouch of golden Syrian hamsters. Although 100% tumor formation was noticed in hamsters treated with DMBA alone, intragastric administration of geraniol, at a dose of 250 mg/kg body weight (b.w.) to DMBA-treated hamster completely prevented the formation of oral tumors. Furthermore, geraniol significantly reduced lipid peroxidation by-products and improved the status of enzymatic and non-enzymatic antioxidants as well as modulated the status of phase I and phase II detoxification enzymes, favoring the excretion of carcinogenic metabolite, during DMBA-induced oral carcinogenesis. The present study concludes that the chemopreventive potential of geraniol relies on its anti-lipid peroxidative and antioxidant function as well as modulatory effects on phase I and II detoxification enzymes to excrete the carcinogenic metabolite, during DMBA-induced hamster buccal pouch carcinogenesis.

Effect of mangrove black tea extract from Ceriops decandra (Griff.) on hematology and biochemical changes in dimethyl benz[a]anthracene-induced hamster buccal pouch carcinogenesis

Effect of the black tea extracted from a mangrove plant species, Ceriops decandra (Griff.) was studied on dimethyl benz[a]anthracene (DMBA)-induced changes in blood hematology and plasma non-enzymatic antioxidants in male hamsters. Hamsters were painted with 0.5% solution of DMBA in liquid paraffin on the right buccal pouch three times in a week up to 14 weeks. Each application treated with 0.4 mg of DMBA. The mangrove black tea extract (MBTE) was administrated orally with 5 mg kg −1 twice a day and then with DMBA on alternate days. Results showed that the DMBA caused a significant ( P < 0.05) decline in the levels of reduced glutathione (GSH), vitamin-C, -E, red blood cells, hemoglobin, mean corpuscular volume and hematocrit; and increase in the levels of WBC, platelets, lymphocytes and neutrophils. The MBTE prevented the DMBA-induced adverse changes significantly in blood and biochemical parameters of the male hamsters. This work concluded that the black tea extracted from the coastal mangrove species C. decandra prevented the DMBA-induced buccal pouch carcinogenesis in hamsters.

Chemopreventive Potential of 18β-glycyrrhetinic Acid: An Active Constituent of Liquorice, in 7,12-dimethylbenz(a)anthracene Induced Hamster Buccal Pouch Carcinogenesis

Chemoprevention, a useful and attractive approach in experimental oncology, helps to investigate the cancer preventive potential of natural products and synthetic entities. Present study evaluated the chemopreventive potential of glycyrrhetinic acid in 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Oral tumor was developed in the buccal pouch of golden Syrian hamsters by painting with DMBA three times a week for 14 weeks. The tumor incidence and the status of phase I and phase II detoxification enzymes were assessed in hamsters treated with DMBA alone and DMBA+glycyrrhetinic acid treated hamsters. One hundred percent tumor formations, which were histopathologically confirmed as well-differentiated squamous cell carcinoma, were observed in hamsters treated with DMBA alone. Also, the status of detoxification enzymes were markedly altered in the liver and buccal mucosa of hamsters treated with DMBA alone. Oral administration ofglycyrrhetinic acid at a dose of 45 mg kg(-1) body weight to hamsters treated with DMBA completely prevented the tumor formation as well as restored the status of detoxification enzymes. Present study thus demonstrated the chemopreventive potential of glycyrrhetinic acid in DMBA induced oral carcinogenesis.

Effective treatment of 7,12‐dimethylbenz(a)anthracene–induced hamster buccal pouch precancerous lesions by topical photosan‐mediated photodynamic therapy

Previous studies found that topical photodynamic therapy (PDT) is very effective for human oral precancerous lesions. This study evaluated whether topical photosan-mediated PDT (topical photosan-PDT), using a 640-nm light-emitting diode (LED) light, is an effective treatment modality for hamster buccal pouch precancerous lesions. Fourteen 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch precancerous lesions were treated with topical photosan-PDT using the 640-nm LED light twice a week. All 14 of the precancerous lesions showed a complete histologically confirmed response to the lesions after an average of 3.79 (range, 3-5) PDT treatments. Normal and precancerous pouch mucosae in the other 4 hamsters received 17 or 19 treatments of topical photosan-PDT showed no cumulative side effects. No recurrence of the lesions was found in these 18 PDT-treated hamsters after a follow-up period of 50 weeks. Our findings indicate that topical photosan-PDT is a very effective treatment modality for DMBA-induced hamster buccal pouch precancerous lesions.

Antitumor Initiating Potential of Rosmarinic Acid in 7,12-Dimethylbenz(a)anthracene-Induced Hamster Buccal Pouch Carcinogenesis

Oral cancer accounts for 40%-50% of all cancers in India. Tobacco and alcohol are the major etiological factors contributing to its pathogenesis. The aim of the present study was to explore the key mechanism behind the inhibitory effects of rosmarinic acid against 7,12-dimethylbenz(a)anthracene (DMBA)-induced oral carcinogenesis by evaluating the status of biochemical markers (lipid peroxidation, antioxidants, and detoxification enzymes) and immunoexpression patterns of p53 and bcl-2 proteins. Oral tumors were developed by painting the buccal pouches of golden Syrian hamsters with 0.5% DMBA in liquid paraffin 3 times a week for 14 weeks. We noticed 100% tumor formation in hamsters treated with DMBA alone, and the tumors were histopathologically confirmed as well-differentiated squamous cell carcinoma. Oral administration of rosmarinic acid (100 mg/kg body wt) to DMBA-treated hamsters completely prevented the tumor formation. In addition, rosmarinic acid significantly returned the status of biochemical and molecular markers to near normal range in DMBA-treated hamsters. The results of the present study suggest that rosmarinic acid suppresses oral carcinogenesis by stimulating the activities of detoxification enzymes, improves the status of lipid peroxidation and antioxidants, and downregulates the expression of p53 and bcl-2 during DMBA-induced oral carcinogenesis.

Chemopreventive and antioxidant efficacy of (6)-paradol in 7, 12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis

The present study evaluated the chemopreventive potential of (6)-paradol, a pungent phenolic constituent of ginger, on 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. The mechanistic pathway for the chemopreventive potential of (6)-paradol was evaluated by measuring the status of tumor incidence, volume and burden as well as by analyzing the status of phase II detoxification agents, lipid peroxidation and antioxidants. Oral squamous cell carcinoma was induced in hamster buccal pouches by painting them with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. We observed 100% tumor formation with marked biochemical abnormalities in tumor-bearing animals compared to control animals. Oral administration of 30mg/kg b.w. (6)-paradol to DMBA-treated hamsters on alternate days from DMBA painting for 14 weeks, significantly reduced the formation of tumors and improved the status of detoxification agents, lipid peroxidation and antioxidants. Therefore, the present study suggests that (6)-paradol has potent chemopreventive, anti-lipid peroxidative and antioxidant potentials as well as a modulating effect on phase II detoxification enzyme and reduced glutathione (GSH) in DMBA-induced hamster buccal pouch carcinogenesis.

Evaluation of 3-(4′-(4″-fluorophenyl)-6′-phenylpyrimidin-2′-yl)-2-phenylthiazolidin-4-one for in vivo modulation of biomarkers of chemoprevention in the 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis

A new bis heterocycle comprising both bioactive 2-aminopyrimidine and thiazolidin-4-one nuclei namely 3-(4′-(4″-fluorophenyl)-6′-phenylpyrimidin-2′-yl)-2-phenylthiazolidin-4-one 3 was synthesized, characterized with the help of melting point, elemental analysis, FT-IR, MS, one-dimensional NMR (1H, 13C) spectra and we evaluated the chemopreventive potential of 3-(4′-(4″-fluorophenyl)-6′-phenylpyrimidin-2′-yl)-2-phenylthiazolidin-4-one based on in vivo inhibitory effects on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Administration of 3 effectively suppressed oral carcinogenesis initiated with DMBA as revealed by the reduced incidence of neoplasms. Lipid peroxidation, glutathione (GSH) content, and the activities of glutathione peroxidase (GPx), glutathione S-transferase (GST) were used to biomonitor the chemopreventive potential of 3. Lipid peroxidation was found to be significantly decreased, whereas GSH, GPx, GST, and GGT were elevated in the oral mucosa of tumor-bearing animals. Our data suggest that 3 may exert its chemopreventive effects in the oral mucosa by modulation of lipid peroxidation and enhancing the levels of GSH, GPx, and GST.

Clerodendron inerme protects cellular integrity during 7,12-dimethylbenz[A]-anthracene induced hamster buccal pouch carcinogenesis.

Aim of the present study was to investigate the protective effect of Clerodendron inerme on cellular integrity by measuring the status of glycoconjugates, lipids, osmotic fragility, and membrane bound enzyme activity in 7,12-dimethylbenz (a) anthracene (DMBA)-induced oral carcinogenesis. Oral squamous cell carcinoma was induced in the buccal pouch of Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin thrice a week for 14 weeks. The levels of glycoconjugates, lipids, osmotic fragility and membrane bound enzyme activity were analyzed by using specific colorimetric methods. We observed 100% tumor formation in DMBA painted hamsters. Altered glycoconjugates and lipid pattern were observed in DMBA painted hamsters as compared to control hamsters. Erythrocytes from DMBA painted hamsters were more fragile than those from control hamsters. The activity of membrane bound enzyme (Na(+) K(+) ATPase) decreased in DMBA painted hamsters as compared to control hamsters. Oral administration of aqueous leaf extract of Clerodendron inerme (CiALet) at a dose of 500 mg/kg body weight significantly prevented the tumor formation and histopathological abnormalities as well as normalized the above said biochemical variables in DMBA painted hamsters. Our results thus demonstrate the protective effect of Clerodendron inerme on cellular integrity during DMBA induced oral carcinogenesis.

Modifying Effects of Piper longum on Cell Surface Abnormalities in 7, 12-dimethylbenz(A)Anthracene Induced Hamster Buccal Pouch Carcinogenesis

Modifying Effects of Piper longum on Cell Surface Abnormalities in 7, 12-dimethylbenz(A)Anthracene Induced Hamster Buccal Pouch Carcinogenesis

Modifying Effects of Annona squamosa on Glycoconjugates Levels in 7,12-dimethylbenz(a)Anthracene Induced Hamster Buccal Pouch Carcinogenesis

Modifying Effects of Annona squamosa on Glycoconjugates Levels in 7,12-dimethylbenz(a)Anthracene Induced Hamster Buccal Pouch Carcinogenesis

Enhancement of Erythrocyte Antioxidants by Green and Black Tea Polyphenols During 7,12-Dimethylbenz[a]anthracene-Induced Hamster Buccal Pouch Carcinogenesis

We evaluated the comparative chemopreventive efficacy of green tea polyphenols (polyphenon-E) and black tea polyphenols (polyphenon-B) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Lipid peroxidation, reduced and oxidized glutathione (GSH and GSSG, respectively), and the GSH-dependent enzymes glutathione peroxidase and glutathione S-transferase in the erythrocytes were used as biomarkers of chemoprevention. Enhanced lipid peroxidation in erythrocytes of DMBA-treated animals was accompanied by a significant decrease in the antioxidant status. Dietary administration of polyphenon-E and -B to DMBA-treated animals significantly decreased the extent of lipid peroxidation and enhanced the levels of GSH, GSH/GSSG ratio, and activities of GSH-dependent enzymes. Our study provides evidence that polyphenon-B is more effective in inhibiting HBP carcinogenesis than polyphenon-E by enhancing the antioxidant status, suggesting that polyphenon-B may have a major impact in the chemoprevention of oral cancer.

Temporal Patterns of Blood Lipidperoxides and Antioxidants in 7,12-dimethylbenz(a)anthracene Induced Hamster Buccal Pouch Carcinogenesis

Temporal Patterns of Blood Lipidperoxides and Antioxidants in 7,12-dimethylbenz(a)anthracene Induced Hamster Buccal Pouch Carcinogenesis

Garlic induces apoptosis during 7,12-dimethylbenz[ a]anthracene-induced hamster buccal pouch carcinogenesis

The apoptosis-inducing capacity of aqueous garlic extract during 7,12-dimethylbenz[ a]anthracene-induced hamster buccal pouch (HBP) carcinogenesis was investigated in male Syrian hamsters using DNA fragmentation and the apoptosis-associated proteins, tissue transglutaminase (tTG) and Bcl-2. Hamsters were divided into four groups of six animals each. Animals in group 1 were painted with a 0.5% solution of DMBA in liquid paraffin on the right buccal pouches three times a week for 14 weeks. Group 2 animals painted with DMBA as in group 1, in addition received 250 mg/kg body weight aqueous garlic extract orally on days alternate to DMBA application. Group 3 animals received garlic extract as in group 2. Group 4 animals received neither DMBA nor garlic extract and served as the control. The experiment was terminated at the end of 14 weeks. Administration of aqueous garlic extract (250 mg/kg body weight) to animals painted with DMBA inhibited DMBA-induced oral carcinogenesis as revealed by the absence of neoplasms, induction of tTG and inhibition of Bcl-2 expression. The results of the present study suggest that garlic may exert its chemopreventive effect by inducing apoptosis.