Chemopreventive potential of esculetin in 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis.

7,12-Dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis is widely preferred to assess the tumor-inhibiting efficacy of the medicinal plants or their constituents. The present study explores the tumor-inhibiting potential of esculetin by utilizing the status of lipid peroxidation by products (thiobarbituric acid reactive substances), antioxidants (vitamin E, reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase), and phase I and phase II detoxification agents as biochemical end points and by using histopathological studies as well in DMBA-induced hamster buccal pouch carcinogenesis. Oral tumors developed in the buccal pouch were subjected to histopathological studies, and were confirmed as oral squamous cell carcinoma. Hamsters treated with DMBA alone showed an abnormal pattern of lipid peroxidation, antioxidants, and detoxification agents as compared to control hamsters. The status of the above-mentioned biochemical markers and histopathological abnormalities were found to be reversed in DMBA + esculetin-treated hamsters. The result of the present study thus indicates the tumor preventive potential of esculetin in DMBA-induced oral carcinogenesis.

Modulating Effect of Enicostemma littorale on the Expression Pattern of Apoptotic, Cell Proliferative, Inflammatory and Angiogenic Markers During 7, 12-Dimethylbenz (a) Anthracene Induced Hamster Buccal Pouch Carcinogenesis.

Enicostemma littorale leaves are traditionally used for the treatment of several diseases, including inflammation and cancer. This study has taken effort to explore the antitumor initiating potential of E. littorale leaves (ElELet) by analyzing the expression pattern of apoptotic (p53, Bcl-2 and Bcl-2 associated X-protein), cell-proliferative (cyclin D1 and proliferating cell nuclear antigen), angiogenic (vascular endothelial growth factor), invasive (matrix metalloproteinase-2 and 9), and inflammatory (NF-κB and cyclooxygenase-2) markers during 7, 12-dimethylbenz (a) anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Oral tumors were induced in the buccal pouches of hamsters using the potent site and organ specific carcinogen, DMBA. DMBA application 3 times a week for 14 weeks resulted in tumor formation in the buccal pouches. Hundred percent tumor formations with dysregulation in the expression pattern of apoptotic, cell proliferative, inflammatory, angiogenic, and invasive markers were observed in the buccal pouches of hamsters treated with DMBA alone. ElELet at a dose of 250 mg/kg body weight orally to DMBA treated hamsters significantly prevented the tumor formation as well as corrected the abnormalities in the expression pattern of above mentioned molecular markers. ElELet thus modulated the expression pattern of all the above mentioned molecular markers in favor of the suppression of cell proliferation occurring in DMBA induced hamster buccal pouch carcinogenesis.

Ursolic acid-loaded chitosan nanoparticles suppress 7,12-dimethylbenz(a)anthracene-induced oral tumor formation through their antilipid peroxidative potential in golden Syrian hamsters.

Oral cancer, a disfiguring and life threatening cancer, significantly affects the day-to-day life of not only the patients but also their family members in terms of life quality and financial burden. India records higher incidence of oral cancer every year and is mainly due to the habituation of tobacco products and alcohol abuse. Delay in diagnosis and treatment influences India's higher incidence of oral cancer, where annually 50,000-60,000 oral carcinoma cases are reported. 7,12-dimethylbenz(a)anthracene (DMBA)-induced cancer in the oral cavity mimics human oral cancer in histopathological, molecular, and morphological aspects, and thus, by using this paradigm, the tumor inhibiting efficacy of medicinal plants or herbs and their components is scientifically validated. Ursolic acid, due to its multiple pharmacological effects, has been attracted, in recent years, for chemoprevention research program. Though, ursolic acid has been shown to have beneficial effects, its poor water solubility and bioavailability hinder to exert its 100% efficacy. Therefore, ursolic acid is encapsulated in either natural or synthetic polymers to enhance its therapeutic efficacy. Chitosan is one of the natural polymers that have been employed in the synthesis of nanoparticles to improve the drug efficacy. The present study has thus chosen ursolic acid-loaded chitosan nanoparticles (UACNP) to assess its anticancer efficacy in the DMBA-induced oral carcinoma. The anticancer efficacy of UACNP in experimental oral carcinogenesis was assessed by employing the status of oxidative markers and detoxification cascade as an end point. DMBA-induced abnormalities in the status of oxidative markers and detoxification cascade were reversed by ursolic acid-loaded chitosan nanoparticles. The tumor inhibiting or suppressing effect of UACNP is thus explored in experimental oral 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.

Effect of curcumin and ferulic acid on modulation of expression pattern of p53 and bcl-2 proteins in 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.

The modulating effect of curcumin and ferulic acid was investigated on expression pattern of apoptosis regulatory p53 and bcl-2 proteins in oral squamous cell carcinoma (OSCC). The OSCC was induced in the buccal pouch of golden Syrian hamster by painting with 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) three-times a week for 14 weeks. The expression pattern of p53 and bcl-2 proteins was analyzed by immunohistochemical staining. We noticed 100% tumor formation in hamsters painted with DMBA alone for 14 weeks. Overexpression of p53 and bcl-2 proteins was observed in the buccal mucosa of tumor-bearing hamsters. Oral administration of curcumin (80 mg/kg body wt) and ferulic acid (40 mg/kg body wt) to DMBA painted hamsters on days alternate to DMBA painting for 14 weeks completely inhibited tumor formation and down-regulated the expression pattern of p53 and bcl-2 proteins. Our results thus demonstrated the protective role of curcumin and ferulic acid on DMBA-induced abnormal expression of p53 and bcl-2 proteins in the buccal mucosa of golden Syrian hamsters.

Protective role of Withaferin-A on immunoexpression of p53 and bcl-2 in 7,12-dimethylbenz(a)anthracene-induced experimental oral carcinogenesis.

Oral cancer, the fifth most frequent cancer worldwide, is a major health problem and accounts for highest morbidity and mortality in human populations. This form of cancer accounts for 40-50% of all cancers in developing countries including India. Despite recent advancement in the treatment, imaging and diagnosis of oral carcinoma, a 5-year survival and mortality rate for this cancer is still at 50%. Our aim was to study the protective effect of Withaferin-A on molecular pathogenesis of oral cancer by evaluating the immunoexpression of p53 and bcl-2 proteins. Oral squamous cell carcinoma was developed in the left buccal pouch of golden Syrian hamsters by painting with 0.5% 7,12-dimethylbenz(a)anthracene (DMBA), three times a week for 14 weeks. We observed 100% tumor formation with high tumor volume and burden in the DMBA alone painted hamsters as compared to control hamsters. We also observed markedly altered expression of p53 and bcl-2 proteins in tumor tissues of oral cancer bearing hamsters. Oral administration of Withaferin-A to DMBA-painted hamsters not only completely prevented oral squamous cell carcinoma formation but also significantly prevented the alterations of p53 and bcl-2 expressions. Our results thus suggest that Withaferin-A has significant protective role against DMBA induced molecular alterations in the buccal mucosa of golden Syrian hamsters.

Antigenotoxic effect of genistein against 7,12-dimethylbenz[a]anthracene induced genotoxicity in bone marrow cells of female Wistar rats.

Carcinogen induced mutation in somatic cells leads to genetic instability, which is considered as an important facet of carcinogenesis. Agents that inhibit DNA adduct formation, stimulate DNA repair mechanisms, and possess antioxidant functions are considered as antigenotoxic agents. Genistein, the major isoflavone of soy products, protects animals against experimentally induced mammary and prostate cancers. 7,12-Dimethylbenz[a]anthracene (DMBA), a potent site-specific carcinogen, induce mutations in DNA through its active metabolite, dihydrodiol epoxide, what is a crucial step in cancer initiation. The antigenotoxic effect of genistein against DMBA-induced genotoxicity has been investigated in the present study by analyzing the frequency of micronucleated polychromatic erythrocytes (MnPCEs) and chromosomal aberrations as cytogenetic end-points. The status of lipid peroxidation, antioxidants and detoxication agents were used as biochemical end-points to assess the antigenotoxic effect of genistein. Elevated MnPCEs frequency, marked chromosomal aberrations and enhanced status of lipid peroxidation, antioxidants and detoxication agents were observed in DMBA-treated animals. Oral pretreatment of genistein (20 mg/kg b.w.) for 5 days to DMBA-treated animals significantly reduced the frequency of micronucleus formation and chromosomal abnormalities as well as reversed the status of biochemical variables. Our results suggest that genistein has potent antigenotoxic effect against DMBA-induced genotoxicity.

Chemopreventive potential of piperine in 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis in Swiss albino mice.

The chemopreventive potential of orally administered piperine was studied in Swiss albino mice against 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin carcinogenesis. The mechanistic pathway for the chemopreventive potential of piperine was evaluated by analysing the status of phase I and phase II detoxification agents, lipid peroxidation by-products and antioxidants during DMBA-induced skin carcinogenesis. Skin squamous cell carcinoma was induced in the shaved back of mice, by painting with DMBA (25µg in 0.1ml acetone/mouse) two times weekly for 8 weeks. We observed severe hyperplasia, dysplasia, and well-differentiated squamous cell carcinoma in the 8th, 10th and 15th week of experimental period respectively in mice treated with DMBA alone. Marked alterations in the status of phase I and phase II detoxification agents, lipid peroxidation by-products and antioxidants were observed in tumor bearing mice. Oral administration of piperine (50mgkg(-1) body weight) by gastric gavage significantly prevented the formation of skin tumors during DMBA-induced mouse skin carcinogenesis. Also, piperine administration brought back the status of phase I and phase II detoxification agents, lipid peroxidation by-products and antioxidants to near normal range in DMBA treated mice. The present study thus demonstrates that piperine has significant suppressing effect on cell proliferation during DMBA-induced mouse skin carcinogenesis. The chemopreventive potential of piperine is probably due to its modulating effect on the status of lipid peroxidation, antioxidants and detoxification agents during DMBA-induced skin carcinogenesis.

Antigenotoxic Effects of Curcumin and Piperine Alone or in Combination Against 7,12-Dimethylbenz(a)anthracene Induced Genotoxicity in Bone Marrow of Golden Syrian Hamsters.

ABSTRACT The present study investigates the effect of curcumin and piperine alone or in combination against 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in the bone marrow of hamsters. The antigenotoxic effect was evaluated by analyzing the frequency of micronucleated polychromatic erythrocytes (MnPCEs) and chromosomal aberrations. Genotoxicity was induced in experimental hamsters by single intraperitoneal injection of DMBA (30 mg/kg b.w). Oral pretreatment of curcumin (80 mg/kg b.w), piperine (50 mg/kg b.w), and curcumin (80 mg/kg b.w) + piperine (50 mg/kg b.w), respectively, for 5 days, significantly reduced the frequency of MnPCEs and the percentage of chromosomal aberrations in the bone marrow of hamsters. The results suggest that cucumin and piperine in combination have a potent antigenotoxic effect as compared to either agent alone in DMBA-induced genotoxicity in golden Syrian hamsters.

Tumor Preventive Efficacy of Emodin in 7,12-Dimethylbenz[a]Anthracene-Induced Oral Carcinogenesis: a Histopathological and Biochemical Approach.

The aim of the present study is to focus the chemopreventive potential of Emodin during 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Tumors were developed in the buccal pouches of golden Syrian hamsters by painting with 0.5% DMBA thrice a week for 14 weeks. The status of lipid peroxidation, antioxidants and detoxification agents were utilized as biochemical endpoints and the expression pattern of apoptotic proteins was employed as molecular endpoints in addition to the histopathological studies, to substantiate the anticancer potential of Emodin. Hamsters treated with DMBA + Emodin revealed mild to moderate precancerous lesions such as hyperplasia and dysplasia whereas 100% tumor formation was noticed in hamsters treated with DMBA alone. Also, Emodin treatment modulated the status of lipid peroxidation, antioxidants, phase I and II detoxification agents and apoptotic proteins in favor of the inhibition/reversal/suppression of the oral tumorigenesis in DMBA treated hamsters. The present study thus concludes that the chemopreventive potential of Emodin relies on its pro-apoptotic and antioxidant efficacy during DMBA induced hamster buccal pouch carcinogenesis.

Diosmin reduces cell viability of A431 skin cancer cells through apoptotic induction.

OBJECTIVES: Aim of the present study was to evaluate the in vitro cytotoxic potential of the diosmin in A431 skin cancer cells. MATERIALS AND METHODS: The cytotoxic (anti-cell proliferative) potential of diosmin in A431 cells was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (cell viability), dual staining (apoptotic induction), dichloro-dihydro-fluorescein diacetate assay (reactive oxygen species [ROS] generation), DNA fragmentation study, Western blotting analysis (apoptotic markers expression) and flow cytometry (cell cycle arrest). RESULTS: Diosmin reduced the cell viability of A431 cells in a dose-dependent fashion and the inhibitory concentration 50% value was attained at 45 µg/ml using MTT assay. Diosmin at a concentration of 45 µg/ml generated excessive ROS in A431 cells, as compared to untreated cells. Diosmin treated A431 cells also revealed multiple DNA fragments than the untreated cells. Diosmin upregulated the expression of p53, caspases 3 and 9 and downregulated the expression of Bcl-2, matrix metalloproteinases-2 and 9 in A431 cells. CONCLUSION: The cytotoxic or anti-cell proliferative potential of diosmin is due to its ROS-mediated apoptotic induction potential, as well as due to its role in the inhibition of invasion in the A431 cells.

EMODIN DOWNREGULATES CELL PROLIFERATION MARKERS DURING DMBA INDUCED ORAL CARCINOGENESIS IN GOLDEN SYRIAN HAMSTERS.

BACKGROUND: Cell-cycle disruption is the major characteristic features of neoplastic transformation and the status of cell-cycle regulators can thus be utilized to assess the prognostic significance in patients with cancer. The PCNA, cyclin D1, CDK4, CDK6 and survivin expression in the buccal mucosa was utilized to evaluate the Emodin efficacy on abnormal cell proliferation during 7,12-dimethylbenz(a)anthracene (DMBA) induced oral carcinogenesis in golden Syrian hamsters. MATERIALS AND METHODS: Topical application of DMBA, three times a week for 14 weeks, on the hamsters' buccal pouches developed well differentiated squamous cell carcinoma. RESULTS: Cyclin D1 and PCNA over-expression and up-regulation of CDK4, CDK6 and survivin were noticed in the buccal mucosa of hamsters treated with DMBA alone. Emodin administration (50mg/kg b.w) orally to hamsters treated with DMBA down-regulated the expression of cell proliferation markers in the buccal mucosa. CONCLUSIONS: The anti-cell proliferative role of Emodin is owing to its modulating efficacy on cell-cycle markers towards the tumor suppression during DMBA induced oral carcinogenesis.

EMODIN EFFICACY ON THE AKT, MAPK, ERK AND DNMT EXPRESSION PATTERN DURING DMBA-INDUCED ORAL CARCINOMA IN GOLDEN SYRIAN HAMSTERS.

BACKGROUND: The present study has evaluated the Emodin efficacy on the Akt, MAPK, ERK and DNMT expression pattern during 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinoma in golden Syrian hamsters, in order to explore its antitumor potential. MATERIALS AND METHODS: Oral tumors were developed in the buccal pouches of golden Syrian hamsters using the carcinogen, DMBA. RESULTS: While the incidence of tumor formation was 100% in hamsters treated with DMBA alone, the tumor formation was not noticed in DMBA+ Emodin treated hamsters. Also, Emodin reduced the severity of precancerous pathological lesions such as dysplasia, in the hamsters treated with DMBA. Emodin administration corrected the abnormalities in the expression pattern of Akt, MAPK, ERK and DNMT in the buccal mucosa of hamsters treated with DMBA. CONCLUSIONS: The present study thus suggests that the tumor preventive potential of Emodin is partly related to its modulating effect on the Akt, MAPK, ERK and DNMT expression pattern, as these molecular markers have a pivotal role in the process of cell proliferation, inflammation, invasion, and apoptosis.

The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease: A Mini Review.

Neurodegenerative diseases affect not only the life quality of aging populations, but also their life spans. All forms of neurodegenerative diseases have a massive impact on the elderly. The major threat of these brain diseases includes progressive loss of memory, Alzheimer's disease (AD), impairments in the movement, Parkinson's disease (PD), and the inability to walk, talk, and think, Huntington's disease (HD). Oxidative stress and mitochondrial dysfunction are highlighted as a central feature of brain degenerative diseases. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, has been known to play a vital role in the pathophysiology of neurodegenerative diseases including AD, PD, and HD. A large number of studies have utilized oxidative stress biomarkers to investigate the severity of these neurodegenerative diseases and medications are available, but these only treat the symptoms. In traditional medicine, a large number of medicinal plants have been used to treat the symptoms of these neurodegenerative diseases. Extensive studies scientifically validated the beneficial effect of natural products against neurodegenerative diseases using suitable animal models. This short review focuses the role of oxidative stress in the pathogenesis of AD, PD, and HD and the protective efficacy of natural products against these diseases.

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.

OBJECTIVE: Malignant 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 METHODS: Oral 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. RESULTS: Oral administration of apigenin at a dose of 2.5mg/kgbw prevented the deregulation of the above mentioned molecular markers in hamsters treated with DMBA. CONCLUSION: Our results thus suggest that apigenin exhibited anti-cell proliferative, anti-inflammatory, anti-angiogenic and apoptotic potential during DMBA-induced hamster buccal pouch carcinogenesis.

Chemopreventive efficacy of naringenin-loaded nanoparticles in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis.

Nanochemoprevention has been introduced recently as a novel approach for improving phytochemicals bioavailability and anti-tumor effect. The present study is designed to evaluate the chemopreventive efficacy of prepared naringenin-loaded nanoparticles (NARNPs) relative to efficacy of free naringenin (NAR) against 7,12-dimethyl benz(a)anthracene (DMBA)-induced oral carcinogenesis by evaluating the status of lipid peroxidation, antioxidants and immunoexpression patterns of proliferating cell nuclear antigen (PCNA) and p53 proteins. Transmission electron microscope (TEM) and dynamic light scattering (DLS) investigations have confirmed a narrow size distribution of the prepared nanoparticles (40-90 nm) with ~88 % encapsulation efficiency. Oral squamous cell carcinoma (OSCC) was 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. DMBA painted animals revealed the morphological changes, hyperplasia, dysplasia and well-differentiated squamous cell carcinoma. Moreover, the status of lipid peroxidation, antioxidants and immunoexpression of PCNA and p53 were significantly altered during DMBA-induced oral carcinogenesis. Oral administration of NARNPs (50 mg NAR/kg body weight/day) to DMBA-treated animals completely prevented the tumor formation as compared to the free NAR and significantly reduced the degree of histological lesions, in addition to restoration of the status of biochemical and molecular markers during oral carcinogenesis. In addition, NARNPs have more potent anti-lipid peroxidative, antiproliferative effect and antioxidant potentials compared to free NAR in DMBA-induced oral carcinogenesis. In conclusion, the present study suggests that NARNPs could be a potentially useful drug carrier system for targeted delivery of naringenin for cancer chemoprevention.

Anti-cell proliferative and anti-angiogenic potential of andrographolide during 7,12- dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis.

Our aim was to explore anti-cell proliferative and anti-angiogenic potential of andrographolide by analyzing the expression pattern of cell proliferative (PCNA, Cyclin D1) and angiogenic (VEGF) markers during 7, 12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. DMBA painting three times a week for 14 weeks in the buccal pouch of golden Syrian hamsters resulted in oral tumors which were histopathologically diagnosed as well differentiated squamous cell carcinoma. Immunohistochemical (PCNA, VEGF) and RT-PCR (Cyclin D1) studies revealed over expression of PCNA, VEGF and Cyclin D1 in the buccal mucosa of hamsters treated with DMBA alone. Oral administration of andrographolide at a dose of 50 mg/kg bw to hamsters treated with DMBA not only suppressed the histological abnormalities but also down regulated the expression of PCNA, VEGF and Cyclin D1. The results of the present study suggest that andrographolide suppressed tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative and anti-angiogenic potential.

Saffron reduction of 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.

Our aim was to investigate the chemopreventive potential of saffron in DMBA-induced hamster buccal pouch carcinogenesis. Assessment was by monitoring the percentage of tumor bearing hamsters, tumor size as well as the status of detoxification agents, lipid peroxidation and antioxidants. Oral squamous cell carcinomas were induced in the buccal pouch of Syrian golden hamsters by painting them with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. We observed 100% oral tumor formation with severe histopathological abnormalities in all the hamsters treated with DMBA alone, activities of phase I and phase II detoxification enzymes, lipid peroxidation and antioxidants being significantly altered. Though oral administration of saffron completely prevented the formation of tumors, we noticed severe hyperplasia and dysplasia in hamsters treated with DMBA, suggesting that tumors might eventually develop. Oral administration of saffron return detoxification enzymes, lipid peroxidation and antioxidants to normal ranges. The chemopreventive potential of saffron thus is likely due to antioxidant properties and modulating effects on detoxification in favour of the excretion of carcinogenic metabolites during DMBA-induced hamster buccal pouch carcinogenesis.

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.

Berberine prevents 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis: a biochemical approach.

Chemoprevention, a novel and useful approach in experimental oncology, deals with the prevention, suppression, or inhibition of carcinogenesis using natural or synthetic entities. This study evaluated the chemopreventive potential of berberine on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral squamous cell carcinoma was 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. Tumor incidence, tumor volume, tumor burden, phase I and phase II carcinogen detoxification agents, lipid peroxidation, antioxidant status, and histopathological changes were assessed in hamsters treated with DMBA alone and in DMBA+berberine-treated animals. Hundred percent tumor incidences with an imbalance in carcinogen-metabolizing enzymes and cellular redox status were observed in hamsters treated with DMBA alone. Oral administration of berberine at a dose of 75 mg/kg body weight (bw) to DMBA-treated hamsters completely prevented tumor incidence and restored the status of the above-mentioned biochemical markers. Berberine, a traditional drug from Southeast Asia, shows promising chemopreventive efficacy in hamster buccal pouch carcinogenesis.