Asokan Manimaran

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.

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.

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.

Enicostemma littorale prevents tumor formation in 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis

Oral cancer is one of the most common malignancies worldwide, and India has recorded the highest annual incidence of oral cancer in comparison with other countries. Altered lipid peroxidation and antioxidant status along with defect in detoxification cascade have been implicated in the pathogenesis of several cancers including oral cancer. The aim of this study was to investigate the chemopreventive potential of ethanolic extract of Enicostemma littorale leaves (ElELet) in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral tumor was developed in the buccal pouches of male golden Syrian hamsters by painting with 0.5% DMBA three times a week for 14 weeks. We observed 100% tumor formation with increase in tumor volume and tumor burden in the hamsters treated with DMBA alone. Imbalance in phase I (cytochrome P450 and cytochrome b5) and phase II (glutathione reductase, glutathione-S-transferase, glutathione, and Deoxythymidine-diaphorase (DT)-diaphorase) detoxification agents and lipid peroxidation by-products (thiobarbituric acid reactive substances) and antioxidant (superoxide dismutase, catalase, glutathione peroxidase, and vitamins E and C) status was noticed in hamsters treated with DMBA alone. Oral administration of ElELet at a dose of 250 mg/kg body weight to hamsters treated with DMBA significantly prevented both precancerous and cancerous lesions in the oral cavity. ElELet modulated the status of phase I and II detoxification agents and antioxidants in favor of the suppression of oral carcinogenesis. This study thus suggests that E. littorale might have inhibited the oral carcinogenesis in DMBA-treated hamsters through its antioxidant potential. The present findings are also substantiated by histological studies during DMBA-induced oral carcinogenesis.

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.

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.

Modulating Effect of Ferulic Acid on NF-kB, COX-2 and VEGF Expression Pattern During 7, 12-Dimethylbenz(a)anthracene Induced Oral Carcinogenesis

Ferulic acid, a natural antioxidant, has the potential to prevent inflammation and to modulate angiogenesis in both in vivo and in vitro models. The present study has investigated the modulating effect of ferulic acid on the expression pattern of COX-2, NF-B and VEGF during 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Over expression of COX-2, NF-B and VEGF was noticed in the oral tumor tissues of hamsters treated with DMBA. Oral administration of ferulic acid at a dose of 40 mg/kg body weight to hamsters treated with DMBA completely prevented the tumor formation and downregulated the expression of COX-2, NF-B and VEGF during DMBA induced oral carcinogenesis. The present results suggest that ferulic acid might have suppressed oral tumor formation by down regulating the expression of COX-2, NF-B and VEGF 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.