Pentoxifylline induces caspase-dependent apoptosis in colorectal cancer cells
Background: Colorectal cancer is a leading cause of mortality worldwide. Resistance of this cancer to the available chemotherapeutic agents creates a need to develop new therapeutic agents. Pentoxifylline (PTX) has been shown to have anticancer effects on multiple cancer types. Objective: In this st...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Informatics in Medicine Unlocked |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S235291482200140X |
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| author | Belal A. Al-Husein Nizar M. Mhaidat Karem H. Alzoubi Ghadeer M. Alzoubi Mohammad A.Y. Alqudah Abla M. Albsoul-Younes Sina M. Matalqah |
| author_facet | Belal A. Al-Husein Nizar M. Mhaidat Karem H. Alzoubi Ghadeer M. Alzoubi Mohammad A.Y. Alqudah Abla M. Albsoul-Younes Sina M. Matalqah |
| author_sort | Belal A. Al-Husein |
| collection | DOAJ |
| description | Background: Colorectal cancer is a leading cause of mortality worldwide. Resistance of this cancer to the available chemotherapeutic agents creates a need to develop new therapeutic agents. Pentoxifylline (PTX) has been shown to have anticancer effects on multiple cancer types. Objective: In this study, we evaluated the anticancer effect of PTX in CRC cells. Methods: We measured PTX's effect on cell proliferation using the MTT assay and on cell death induction by PI staining/flowcytometry. We also assessed the effect of treatment on mitochondrial membrane potential (MMP). Results: We found that PTX arrested the growth SW480 CRC cells with a peak effect plateauing at 10 mM of PTX after 72 h of treatment. Surprisingly, similar effect wasn't noticed in HCT-116 cells. Similar pattern of effect was noticed on apoptosis of both cell lines, as PTX induced more apoptosis on SW480 cells with no similar effect on HCT-116 cells. Studies using variable caspase inhibitors showed involvement of primarily capsase-9, as well as caspases-2 and -3 but not capsase-8. PTX also induced MMP changes leading to caspase-dependent apoptotic cell death. In addition to that, results indicated that apoptosis was caspase-dependent and was mediated through the mitochondria. Conclusion: These findings indicate that PTX has a promising antitumor activity against CRC cells and warrants further clinical evaluation. |
| first_indexed | 2024-04-14T04:41:53Z |
| format | Article |
| id | doaj.art-7c81ee38fcba4a1a903345eb861611bc |
| institution | Directory Open Access Journal |
| issn | 2352-9148 |
| language | English |
| last_indexed | 2024-04-14T04:41:53Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Informatics in Medicine Unlocked |
| spelling | doaj.art-7c81ee38fcba4a1a903345eb861611bc2022-12-22T02:11:38ZengElsevierInformatics in Medicine Unlocked2352-91482022-01-0131100997Pentoxifylline induces caspase-dependent apoptosis in colorectal cancer cellsBelal A. Al-Husein0Nizar M. Mhaidat1Karem H. Alzoubi2Ghadeer M. Alzoubi3Mohammad A.Y. Alqudah4Abla M. Albsoul-Younes5Sina M. Matalqah6Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; Corresponding author. Associate Professor in Clinical and Experimental Therapeutics Department of Clinical Pharmacy Faculty of Pharmacy Jordan University of Science and Technology P.O. Box 3030, Irbid, 22110, Jordan.Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, JordanDepartment of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates; Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, JordanDepartment of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, JordanDepartment of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates; Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, JordanDepartment of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, The University of Jordan, Amman, JordanPharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-ahliyya Amman University, Amman 19328, JordanBackground: Colorectal cancer is a leading cause of mortality worldwide. Resistance of this cancer to the available chemotherapeutic agents creates a need to develop new therapeutic agents. Pentoxifylline (PTX) has been shown to have anticancer effects on multiple cancer types. Objective: In this study, we evaluated the anticancer effect of PTX in CRC cells. Methods: We measured PTX's effect on cell proliferation using the MTT assay and on cell death induction by PI staining/flowcytometry. We also assessed the effect of treatment on mitochondrial membrane potential (MMP). Results: We found that PTX arrested the growth SW480 CRC cells with a peak effect plateauing at 10 mM of PTX after 72 h of treatment. Surprisingly, similar effect wasn't noticed in HCT-116 cells. Similar pattern of effect was noticed on apoptosis of both cell lines, as PTX induced more apoptosis on SW480 cells with no similar effect on HCT-116 cells. Studies using variable caspase inhibitors showed involvement of primarily capsase-9, as well as caspases-2 and -3 but not capsase-8. PTX also induced MMP changes leading to caspase-dependent apoptotic cell death. In addition to that, results indicated that apoptosis was caspase-dependent and was mediated through the mitochondria. Conclusion: These findings indicate that PTX has a promising antitumor activity against CRC cells and warrants further clinical evaluation.http://www.sciencedirect.com/science/article/pii/S235291482200140XPentoxifyllineCaspaseApoptosisColorectal cancerCells |
| spellingShingle | Belal A. Al-Husein Nizar M. Mhaidat Karem H. Alzoubi Ghadeer M. Alzoubi Mohammad A.Y. Alqudah Abla M. Albsoul-Younes Sina M. Matalqah Pentoxifylline induces caspase-dependent apoptosis in colorectal cancer cells Informatics in Medicine Unlocked Pentoxifylline Caspase Apoptosis Colorectal cancer Cells |
| title | Pentoxifylline induces caspase-dependent apoptosis in colorectal cancer cells |
| title_full | Pentoxifylline induces caspase-dependent apoptosis in colorectal cancer cells |
| title_fullStr | Pentoxifylline induces caspase-dependent apoptosis in colorectal cancer cells |
| title_full_unstemmed | Pentoxifylline induces caspase-dependent apoptosis in colorectal cancer cells |
| title_short | Pentoxifylline induces caspase-dependent apoptosis in colorectal cancer cells |
| title_sort | pentoxifylline induces caspase dependent apoptosis in colorectal cancer cells |
| topic | Pentoxifylline Caspase Apoptosis Colorectal cancer Cells |
| url | http://www.sciencedirect.com/science/article/pii/S235291482200140X |
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