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 the NSAIDs are efficient in controlling the proliferation of neoplasm in the colon.
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 the NSAIDs are efficient in controlling the proliferation of neoplasm in the colon.
Authors: Jeff Hirst; Harsh B Pathak; Stephen Hyter; Ziyan Y Pessetto; Thuc Ly; Stefan Graw; Devin C Koestler; Adam J Krieg; Katherine F Roby; Andrew K Godwin Journal: Cancer Res Date: 2018-06-11 Impact factor: 12.701