Chemopreventive Effects of Non-steroidal Anti-inflammatory Drugs in Early Neoplasm of Experimental Colorectal Cancer: an
- PDF / 641,764 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 109 Downloads / 146 Views
ORIGINAL RESEARCH
Chemopreventive Effects of Non-steroidal Anti-inflammatory Drugs in Early Neoplasm of Experimental Colorectal Cancer: an Apoptosome Study Vivek Vaish & Lalita Tanwar & Jasmeet Kaur & Sankar Nath Sanyal
Published online: 13 July 2010 # Springer Science+Business Media, LLC 2010
Abstract Purpose Apoptosis is a highly regulated mechanism of cell death where pro-apoptotic proteins and caspases play an important role. Activation of pro-caspases at a definite time is essential to control the whole caspase cascade. Mitochondrion contains some pro-apoptotic proteins, which need to come out in cytoplasm for apoptotic function such as Cytochrome c (Cyt c), while the Bcl-2 protein family works as the guard of mitochondrial membrane and prevents the escape of Cyt c. Once Cyt c is out in cytoplasm, it binds with Apaf-1 (another pro-apoptotic protein also essential for proper cell differentiation) and pro-caspase-9, forming the Apoptosome complex. In this study, the role of two non-steroidal anti-inflammatory drugs (NSAIDs), Diclofenac and Celecoxib, in experimentally induced early neoplasm of colon via apoptosome mechanism had been studied. It has been recognized that the prolonged use of NSAIDs has its effect on reducing the risk of colorectal cancer through apoptotic pathways. However, the role of NSAIDs in respect of apoptosome is not clear. Methods Western blotting and immunohistochemistry were performed, along with morphological and histological analysis. Results According to the expression levels of Cytochrome c, Apaf-1, Caspases, and Bcl-2, it was observed that NSAIDs do follow the mitochondrial or intrinsic pathway of apoptosis. Conclusion The effects of Diclofenac and Celecoxib on the expression of pro- and anti-apoptotic proteins have been observed, which may constitute the mechanism by which V. Vaish : L. Tanwar : J. Kaur : S. N. Sanyal (*) Department of Biophysics, Panjab University, Chandigarh 160014, India e-mail: [email protected]
the NSAIDs are efficient in controlling the proliferation of neoplasm in the colon. Keywords cytochrome c . Bcl-2 . Apaf-1 . caspases . apoptosome . NSAIDs
Introduction The relative balance between proliferation and apoptosis is responsible for tumor growth. Inhibition of colonic tumor growth cannot be achieved only by decrease in cell proliferation. According to Sinicrope et al. [1], decrease in apoptosis during tumor progression is responsible for colon cancer in humans. Further, in comparison with adenomas, carcinomas have lower rates of apoptosis without any change in proliferation rate. This imbalance in apoptosis and proliferation ratio has a role in tumor development. Initiation of apoptosis in vivo attribute to the antitumor characteristic of non-steroidal anti-inflammatory drugs (NSAIDs) in colon cancer [2, 3]. This has been further confirmed by genetic and pharmacological studies. The anti-tumorigenic properties of NSAIDs are linked with the inhibition of Cyclooxygenase (COX) enzyme, which is a rate-limiting enzyme in Prostaglandin (PG) biosynthesis [4, 5]
Data Loading...
