Abdelaziz, R.F.; Hussein, A.M.; Kotob, M.H.; Weiss, C.; Chelminski, K.; Studenik, C.R.; Aufy, M. The Significance of Cathepsin B in Mediating Radiation Resistance in Colon Carcinoma Cell Line (Caco-2). Int. J. Mol. Sci.2023, 24, 16146.
Abdelaziz, R.F.; Hussein, A.M.; Kotob, M.H.; Weiss, C.; Chelminski, K.; Studenik, C.R.; Aufy, M. The Significance of Cathepsin B in Mediating Radiation Resistance in Colon Carcinoma Cell Line (Caco-2). Int. J. Mol. Sci. 2023, 24, 16146.
Abdelaziz, R.F.; Hussein, A.M.; Kotob, M.H.; Weiss, C.; Chelminski, K.; Studenik, C.R.; Aufy, M. The Significance of Cathepsin B in Mediating Radiation Resistance in Colon Carcinoma Cell Line (Caco-2). Int. J. Mol. Sci.2023, 24, 16146.
Abdelaziz, R.F.; Hussein, A.M.; Kotob, M.H.; Weiss, C.; Chelminski, K.; Studenik, C.R.; Aufy, M. The Significance of Cathepsin B in Mediating Radiation Resistance in Colon Carcinoma Cell Line (Caco-2). Int. J. Mol. Sci. 2023, 24, 16146.
Abstract
Cathepsins (Caths) are lysosomal proteases that participate in various physiological and pathological processes. Accumulating evidence suggests that cathepsins play a multifaceted role in radiotherapy response. Firstly, cathepsins contribute to the remodelling of the tumor microenvironment by degrading extracellular matrix components, promoting angiogenesis, and facilitating tumor invasion and metastasis. Their proteolytic activity influences the tumor's response to radiation by affecting oxygenation, nutrient availability, and immune cell infiltration within the tumor microenvironment. Furthermore, cathepsins have been implicated in DNA damage repair processes, including non-homologous end joining and homologous recombination. Cathepsin-mediated DNA repair mechanisms can promote radioresistance in cancer cells, limiting the efficacy of radiotherapy. Additionally, cathepsins have been associated with the activation of prosurvival signalling pathways, such as PI3K/Akt and NF-κB, which can confer resistance to radiation-induced cell death.
Radiotherapy plays a crucial role in the treatment of various malignancies. However, the effectiveness of radiotherapy can be limited by intrinsic or acquired resistance mechanisms in cancer cells. In recent years, there has been growing interest in understanding the role of cathepsins, a family of proteases, in modulating the response of tumor cells to radiotherapy.
In this study, we shed light on the regulation and expression of cathepsin B in colon carcinoma cell line (Caco-2) before and after exposure to radiation were investigated. Radiation-induced upregulation of cathepsin B in dose-independent manner. Proteolytic inhibition of cathepsin B by cathepsin B specific inhibitor CA074 has increased the cytotoxic effect of ionizing irradiation in caco-2 cells. Similar results were also obtained after cathepsin B knockout by CRISPR CAS9. These results showed that cathepsin B could contribute to ionizing radiation resistance and abolishing of cathepsin B either by inhibition its proteolytic activity or expression has increased in caco-2 cells susceptibility to ionizing irradiation.
Biology and Life Sciences, Biochemistry and Molecular Biology
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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