Enhancement of Radiation Sensitivity by Cathepsin L Suppression in Colon Carcinoma Cells
Cancer is one of the main causes of death globally. Radiotherapy/Radiation therapy (RT) is one of the most common and effective cancer treatments. RT utilizes high-energy radiation to damage the DNA of cancer cells, leading to their death or impairing their proliferation. However, radiation resistan...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/23/17106 |
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| author | Ramadan F. Abdelaziz Ahmed M. Hussein Mohamed H. Kotob Christina Weiss Krzysztof Chelminski Tamara Stojanovic Christian R. Studenik Mohammed Aufy |
| author_facet | Ramadan F. Abdelaziz Ahmed M. Hussein Mohamed H. Kotob Christina Weiss Krzysztof Chelminski Tamara Stojanovic Christian R. Studenik Mohammed Aufy |
| author_sort | Ramadan F. Abdelaziz |
| collection | DOAJ |
| description | Cancer is one of the main causes of death globally. Radiotherapy/Radiation therapy (RT) is one of the most common and effective cancer treatments. RT utilizes high-energy radiation to damage the DNA of cancer cells, leading to their death or impairing their proliferation. However, radiation resistance remains a significant challenge in cancer treatment, limiting its efficacy. Emerging evidence suggests that cathepsin L (cath L) contributes to radiation resistance through multiple mechanisms. In this study, we investigated the role of cath L, a member of the cysteine cathepsins (caths) in radiation sensitivity, and the potential reduction in radiation resistance by using the specific cath L inhibitor (Z-FY(tBu)DMK) or by knocking out cath L with CRISPR/Cas9 in colon carcinoma cells (caco-2). Cells were treated with different doses of radiation (2, 4, 6, 8, and 10), dose rate 3 Gy/min. In addition, the study conducted protein expression analysis by western blot and immunofluorescence assay, cytotoxicity MTT, and apoptosis assays. The results demonstrated that cath L was upregulated in response to radiation treatment, compared to non-irradiated cells. In addition, inhibiting or knocking out cath L led to increased radiosensitivity in contrast to the negative control group. This may indicate a reduced ability of cancer cells to recover from radiation-induced DNA damage, resulting in enhanced cell death. These findings highlight the possibility of targeting cath L as a therapeutic strategy to enhance the effectiveness of RT. Further studies are needed to elucidate the underlying molecular mechanisms and to assess the translational implications of cath L knockout in clinical settings. Ultimately, these findings may contribute to the development of novel treatment approaches for improving outcomes of RT in cancer patients. |
| first_indexed | 2024-03-09T01:48:41Z |
| format | Article |
| id | doaj.art-3114b10a1fb445e9be76c1bf90505d97 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T01:48:41Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3114b10a1fb445e9be76c1bf90505d972023-12-08T15:18:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124231710610.3390/ijms242317106Enhancement of Radiation Sensitivity by Cathepsin L Suppression in Colon Carcinoma CellsRamadan F. Abdelaziz0Ahmed M. Hussein1Mohamed H. Kotob2Christina Weiss3Krzysztof Chelminski4Tamara Stojanovic5Christian R. Studenik6Mohammed Aufy7Department of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna, 1090 Vienna, AustriaDepartment of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna, 1090 Vienna, AustriaDepartment of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna, 1090 Vienna, AustriaDepartment of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna, 1090 Vienna, AustriaDivision of Human Health, International Atomic Energy Agency, Wagramer Str. 5, 1400 Vienna, AustriaProgramme for Proteomics, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna, 1090 Vienna, AustriaDepartment of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna, 1090 Vienna, AustriaCancer is one of the main causes of death globally. Radiotherapy/Radiation therapy (RT) is one of the most common and effective cancer treatments. RT utilizes high-energy radiation to damage the DNA of cancer cells, leading to their death or impairing their proliferation. However, radiation resistance remains a significant challenge in cancer treatment, limiting its efficacy. Emerging evidence suggests that cathepsin L (cath L) contributes to radiation resistance through multiple mechanisms. In this study, we investigated the role of cath L, a member of the cysteine cathepsins (caths) in radiation sensitivity, and the potential reduction in radiation resistance by using the specific cath L inhibitor (Z-FY(tBu)DMK) or by knocking out cath L with CRISPR/Cas9 in colon carcinoma cells (caco-2). Cells were treated with different doses of radiation (2, 4, 6, 8, and 10), dose rate 3 Gy/min. In addition, the study conducted protein expression analysis by western blot and immunofluorescence assay, cytotoxicity MTT, and apoptosis assays. The results demonstrated that cath L was upregulated in response to radiation treatment, compared to non-irradiated cells. In addition, inhibiting or knocking out cath L led to increased radiosensitivity in contrast to the negative control group. This may indicate a reduced ability of cancer cells to recover from radiation-induced DNA damage, resulting in enhanced cell death. These findings highlight the possibility of targeting cath L as a therapeutic strategy to enhance the effectiveness of RT. Further studies are needed to elucidate the underlying molecular mechanisms and to assess the translational implications of cath L knockout in clinical settings. Ultimately, these findings may contribute to the development of novel treatment approaches for improving outcomes of RT in cancer patients.https://www.mdpi.com/1422-0067/24/23/17106cancerradiotherapycath Lknockoutinhibitorcolon carcinoma |
| spellingShingle | Ramadan F. Abdelaziz Ahmed M. Hussein Mohamed H. Kotob Christina Weiss Krzysztof Chelminski Tamara Stojanovic Christian R. Studenik Mohammed Aufy Enhancement of Radiation Sensitivity by Cathepsin L Suppression in Colon Carcinoma Cells International Journal of Molecular Sciences cancer radiotherapy cath L knockout inhibitor colon carcinoma |
| title | Enhancement of Radiation Sensitivity by Cathepsin L Suppression in Colon Carcinoma Cells |
| title_full | Enhancement of Radiation Sensitivity by Cathepsin L Suppression in Colon Carcinoma Cells |
| title_fullStr | Enhancement of Radiation Sensitivity by Cathepsin L Suppression in Colon Carcinoma Cells |
| title_full_unstemmed | Enhancement of Radiation Sensitivity by Cathepsin L Suppression in Colon Carcinoma Cells |
| title_short | Enhancement of Radiation Sensitivity by Cathepsin L Suppression in Colon Carcinoma Cells |
| title_sort | enhancement of radiation sensitivity by cathepsin l suppression in colon carcinoma cells |
| topic | cancer radiotherapy cath L knockout inhibitor colon carcinoma |
| url | https://www.mdpi.com/1422-0067/24/23/17106 |
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