Sekar Karthikeyan

Chemopreventive potential of apigenin in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis.

Aim was to investigate the chemopreventive potential of apigenin by analyzing the tumor incidence as well as monitoring lipid peroxidation, antioxidants and phase I and phase II detoxification as biomarkers during DMBA induced hamster buccal pouch carcinogenesis. Oral tumors were developed in the buccal pouches of golden Syrian hamsters using topical application of 0.5% DMBA (DMBA) three times a week for 14weeks. Tumor incidence, tumor volume and burden were measured in hamsters treated with 7,12-dimethylbenz(a)anthracene and DMBA+apigenin (2.5mg/kg body weight) treated hamsters. Oral administration of apigenin not only completely prevented the formation of oral tumors, it also brought back the status of lipid peroxidation, antioxidants and phase I and phase II detoxification agents to near normal range during DMBA induced oral carcinogenesis. The present study thus concludes that apigenin might have inhibited oral carcinogenesis by improving the status of antioxidant defense mechanism and modulated the activities of phase I and phase II detoxification cascade toward increased excretion of active metabolite of DMBA, during DMBA induced hamster buccal pouch carcinogenesis.

Anti-Cell Proliferative Efficacy of Ferulic Acid Against 7, 12-dimethylbenz(a) Anthracene Induced Hamster Buccal Pouch Carcinogenesis

The present study was designed to explore the anti-cell proliferative efficacy of ferulic acid by analysing the expression pattern of cell proliferative markers, proliferating cellular nuclear antigen (PCNA) and cyclin D1, in the buccal mucosa of golden Syrian hamsters treated with 7,12-dimethylbenz(a)anthracene (DMBA). Oral squamous cell carcinomas developed in the buccal pouch of hamsters using topical application of 0.5% DMBA three times a week for 14 weeks. Immunohistochemical (PCNA) and RT-PCR (Cyclin D1) analysis revealed over expression of PCNA and cyclin D1 in the buccal mucosa of hamsters treated with DMBA alone (tumor bearing hamsters). Oral administration of ferulic acid at a dose of 40 mg/kg bw to hamsters treated with DMBA not only completely prevented the tumor formation but also down regulated the expression of PCNA and cyclin D1. The results of the present study thus suggests that ferulic acid might have inhibited tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative potential as evidenced by decreased expression of PCNA and cyclin D1.

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

Introduction: Chemoprevention, an emerging, appealing, and innovative approach in experimental oncology, deals with the inhibition, prevention or suppression of carcinogenesis, using natural products or synthetic derivatives. The aim of the present study is to investigate the chemopreventive potential of chrysin during 7,12-dimethylbenza[a]anthracene (DMBA) - induced hamster buccal pouch carcinogenesis. Materials and Methods: Oral squamous cell carcinoma was developed in the buccal pouch of Syrian golden hamsters by painting them with 0.5 percent DMBA in liquid paraffin thrice a week, for 14 weeks. The status of lipid peroxidation, antioxidants, and phase I and II detoxification agents were utilized as biochemical end points, to assess the chemopreventive efficacy of chrysin in DMBA-induced hamster buccal pouch carcinogenesis. Results: In the present study, 100% tumor formation with marked abnormalities in the status of lipid peroxidation, antioxidants, and detoxification agents was noticed in hamsters treated with DMBA alone. Oral administration of chrysin at a dose of 250 mg/kg bw to DMBA-treated hamsters significantly reduced the tumor incidence and tumor size as well as reverted the status of the above-mentioned biochemical markers during DMBA-induced hamster buccal pouch carcinogenesis. Conclusion: Chrysin has the potential to delay rather than inhibit tumor formation as evidenced by the tumor formation in two of the DMBA + chrysin-treated hamsters, during DMBA-induced hamster buccal pouch carcinogenesis.

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.

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.

An overview of oral carcinogenesis

Cancer, a life-threatening global burden, is characterized by clonality, autonomy, anaplasia, invasion, and metastasis. Each and every year, the incidence of cancer is increasing worldwide. Most of the cancers arise due to changes in the lifestyle, including tobacco, smoking, and alcohol abuse. Although 100 different types of cancers were reported so far worldwide, oral cancer, skin cancer, mammary cancer, lung cancer, and cervical cancer are the most predominant cancers. Cancer of the oral cavity remains life-threatening disease for more than 50% of the newly diagnosed patients. Lack of awareness, delay in diagnosis, and patient′s delay are attributed to the high incidence of oral cancer, despite easy physical examination of the oral cavity. Moreover, the survival outcome of oral cancer patients was not drastically improved despite recent advancement in the treatment of oral cancers. The present review presents the epidemiology and etiology of oral cancer in detail. Furthermore, the biochemical and molecular changes occurring in oral carcinogenesis are also explored. The chemopreventive agents that are evaluated against experimental carcinogenesis are also briefly summarized.

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.

Anti-cell Proliferative, Anti-inflammatory and Anti-angiogenic Potential of Lupeol in 7,12-dimethylbenz(a) Anthracene Induced Hamster Buccal Pouch Carcinogenesis

Aim: Diverse pharmacological and biochemical effects of lupeol have been reported earlier. The present study utilized the immune expression pattern of proliferating cellular nuclear antigen (PCNA), cyclin D1, vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NFkB) to assess the anticancer potential of lupeol in 7,12-dimethylbenz(a) anthracene (DMBA) induced oral carcinogenesis. Methods: Well differentiated squamous cell carcinoma was appeared in the buccal mucosa of hamsters painted with DMBA thrice a week for 14 weeks. The expression pattern of the molecular Original Research Article Manimaran et al.; BJMMR, 6(6): 587-596, 2015; Article no.BJMMR.2015.236 588 markers was analysed using immunohistochemistry (PCNA, VEGF), Real Time PCR (NFkB, cyclin D1) and ELISA (COX-2). Results: We noticed oral tumors in all the hamsters treated with DMBA alone and thus the tumor incidence is 100%. The total number of tumors developed in DMBA alone painted hamsters was 23. Upregulation of cell proliferative (PCNA, cyclin D1), inflammatory (NFkB, COX-2) and angiogenic markers (VEGF) was noticed in oral tumor bearing hamsters. Lupeol administration orally to DMBA painted hamsters completely inhibited the tumor formation (0%) and downregulated the immunoexpression pattern of cell proliferative (PCNA, cyclin D1), inflammatory (NFkB, COX-2) and angiogenic markers (VEGF). Conclusion: The present results suggest that lupeol exhibited antitumor potential through its anticell proliferative, anti-inflammatory and anti-angiogenic potential during DMBA induced oral carcinogenesis.

REDUCED SUSCEPTIBILITY OF MRSA TO VANCOMYCIN

Objective: This study was conducted to observe the antibiogram, vancomycin MIC (Minimum Inhibitory Concentration), and inducible clindamycin resistance in clinical isolates of MRSA (Methicillin-Resistance Staphylococcus aureus ). Methods: Drug resistance pattern was studied by Kirby-Bauer disc diffusion methods. MIC of vancomycin was determined by agar dilution method. Results: MRSA was found to be highly resistant to gentamicin (76%), erythromycin (67.03%) and ciprofloxacin (65.09%) while glycopeptides showed uniform susceptibility. Conclusion: Though there was no drug resistance observed against vancomycin and linezolid, it’s wise to use these antibiotics safely as emerging resistance has been reported for these drugs from all over the world.