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Chemopreventive Effects of Non-steroidal Anti-inflammatory Drugs in Early Neoplasm of Experimental Colorectal Cancer: an Apoptosome Study

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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 the NSAIDs are efficient in controlling the proliferation of neoplasm in the colon.

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Acknowledgements

Financial assistance from the Department of Science and Technology, Govt. of India (SR/SO/BB-05/2008), is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Biophysics, Panjab University, Chandigarh, 160014, India

    Vivek Vaish, Lalita Tanwar, Jasmeet Kaur & Sankar Nath Sanyal

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  1. Vivek Vaish
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  2. Lalita Tanwar
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  4. Sankar Nath Sanyal
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Correspondence to Sankar Nath Sanyal.

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Vaish, V., Tanwar, L., Kaur, J. et al. Chemopreventive Effects of Non-steroidal Anti-inflammatory Drugs in Early Neoplasm of Experimental Colorectal Cancer: an Apoptosome Study. J Gastrointest Canc 42, 195–203 (2011). https://doi.org/10.1007/s12029-010-9188-2

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  • DOI: https://doi.org/10.1007/s12029-010-9188-2

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