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 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.

Ferulic Acid Reduces Cell Viability through Its Apoptotic Efficacy: An In vitro Approach.

Aim: Ferulic acid, a well known dietary phenolic antioxidant, possesses diverse pharmacological and biochemical effects, including anti-inflammatory, hepatoprotective, antidiabetic and anticancer properties. The present study explores the cytotoxic potential of ferulic acid using Hep-2 cell line by analyzing its effect on cell viability, reactive oxygen species generation, apoptotic induction, nuclear damage, DNA fragmentation and expression of apoptosis related proteins. Materials and Methods: The effect of ferulic acid (2.5, 5, 10, 20 and 40 μg/ml) on Hep-2 cells viability for 24 hr was determined by MTT assay. To substantiate the cytotoxic effect of ferulic acid, the intracellular ROS level was determined using DCFH-DA assay; apoptosis by dual staining; nuclear damage by DAPI staining; DNA fragmentation by using agarose gel electrophoresis; apoptosis related proteins by western blotting. Results: Ferulic acid significantly inhibited the Hep-2 cell growth in a dose dependent manner and ferulic acid treated Hep-2 cells exhibited features of apoptosis and increase in nuclear damage and DNA fragmentation. We also observed excess reactive oxygen species generation in ferulic acid treated Hep-2 cells. Apoptosis related proteins (p53, Bcl-2, Bax, Caspase 3 & Caspase 9) were significantly modulated in favour of programmed cell death in ferulic acid treated cells. Conclusion: We thus conclude that the cytotoxic potential of ferulic acid might be due to its role in apoptosis induction, excessive ROS generation and DNA fragmentation in Hep-2 cells.

Effect of curcumin and ferulic acid on modulation of expression pattern of p53 and bcl-2 proteins in 7,12-dimethylbenz[]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[]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.

Terminalia arjuna [Roxb.] modulates circulatory antioxidants on 7,12-dimethylbenz[a]anthracene- induced Hamster buccal pouch carcinogenesis

Oral cancer is the fifth most frequent cancer worldwide and India has recorded the highest incidence [40-50%] of oral malignancy. This study is designed to investigate the effect of aqueous extract of Terminalia arjuna bark [TaBet] on circulatory lipid peroxidation and antioxidant status during 7,12-dimethylbenz[a]anthracene [DMBA]-induced hamster buccal pouch carcinogenesis. Male Syrian golden hamsters painted with 0.5% 7,12-dimethylbenz[a]anthracene on the buccal pouches and developed oral squamous cell carcinoma were included in this study. The enhanced Thiobarbituric acid reactive substances in circulation of tumor-bearing animals was accompanied by a significant decrease in the levels of vitamin C, vitamin E, reduced glutathione, superoxide dismutase, catalase and glutathione peroxidase. Administration of TaBet [500 mg/kg body weight] significantly suppressed DMBA-induced hamster buccal pouch carcinomas, decreased lipid peroxidation and enhanced the levels of antioxidants. The chemopreventive potential of TaBet is probably due to its antilipidperoxidative effect or the presence of some potent bioactive chemopreventive principles in the bark of Terminalia arjuna. The results of the present study indicate that T. arjuna may emerge as a putative chemopreventive agent against oral carcinogenesis