Simon Silvan

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.

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.

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.

Modulating effect of lupeol on the expression pattern of apoptotic markers in 7, 12-dimethylbenz(a)anthracene induced oral carcinogenesis.

Apoptosis, also known as cell suicide or programmed cell death, removes unwanted and genetically damaged cells from the body. Evasion of apoptosis is one of the major characteristic features of rapidly proliferating tumor cells. Chemopreventive agents inhibit or suppress tumor formation through apoptotic induction in target tissues. The aim of the present study was to investigate the pro-apoptotic potential of lupeol during 7,12-dimethylbenz(a) anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Topical application of 0.5% DMBA three times a week for 14 weeks in the buccal pouches of golden Syrian hamsters resulted in oral squamous cell carcinoma. The expression pattern of apoptotic markers was analyzed using immunohistochemistry (p53, Bcl-2, Bax) and ELISA reader (caspase 3 and 9). In the present study, 100% tumor formation with defects in apoptotic markerexpression pattern was noticed in hamsters treated with DMBA alone. Oral administration of lupeol at a dose of 50 mg/kg bw completely prevented the formation oral tumors as well as decreased the expression p53 and Bcl-2, while increasing the expression of Bax and the activities of caspase 3 and 9. The present study thus indicated that lupeol might inhibit DMBA-induced oral tumor formation through its pro-apoptotic potential in golden Syrian hamsters.

Anti-clastogenic potential of carnosic acid against 7,12-dimethylbenz(a) anthracene (DMBA)-induced clastogenesis

Carnosic acid, a primary phenolic compound found in the leaves of rosemary (Rosmarinus officinalis), has diverse pharmacological and biological activities. The aim of the present study was to investigate the anti-clastogenic effect of carnosic acid in DMBA-induced clastogenesis. The frequency of bone marrow micronucleated polychromatic erythrocytes (MnPCEs), chromosomal aberrations (cytogenetic end points), the status of Phase I and II detoxification enzymes, lipid peroxidation by-products and antioxidants (biochemical endpoints) were analyzed to assess the anti-clastogenic effect of carnosic acid in DMBA-induced clastogenesis. Oral pretreatment of carnosic acid for five days to DMBA-treated hamsters significantly protected DMBA-induced clastogenesis as well as biochemical abnormalities. Although the exact mechanism of anti-clastogenic effects of carnosic acid is unclear, the antioxidant potential and effect on modulation of Phase I and II detoxification enzymes could play a possible role.

Effects of Punica granatum Flowers on Carbohydrate Metabolizing Enzymes, Lipid Peroxidation and Antioxidants Status in Streptozotocin Induced Diabetic Rats

The mechanistic pathway for the antidiabetic efficacy of ethanolic extract of Punica granatum flowers (PgEFet) has been investigated by measuring the status of blood glucose, plasma insulin, carbohydrate metabolizing enzymes, lipid peroxidation and antioxidants as biochemical end points in streptozotocin induced diabetic rats. Diabetes mellitus was induced by single intraperitoneal injection of streptozotocin (50mg/kg b.w) in albino Wistar rats. Oral administration of PgEFet (400mg/kg b.w) by gastric gavage to diabetic animals significantly reduced the level of blood glucose and increased the level of plasma insulin as well as reverted the disturbed activities of carbohydrate metabolizing enzymes to near normal pattern. Also, PgEFet exhibited potent anti-lipid peroxidative and antioxidant function in strepto- zotocin induced diabetic rats. The present study thus concludes that the antidiabetic efficacy of Punica granatum flowers in streptozotocin induced diabetic rats relies on its modulating effect on carbohydrate metabolizing enzymes as well as its anti-lipid peroxidative and antioxidant potential.

WITHDRAWN: Apigenin: A potent antigenotoxic and anticlastogenic agent

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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.