A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying Mechanisms
Chemoresistance causes cancer relapse and metastasis, thus remaining the major obstacle to cancer therapy. While some light has been shed on the underlying mechanisms, it is clear that chemoresistance is a multifaceted problem strictly interconnected with the high heterogeneity of neoplastic cells....
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/43/1/14 |
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| author | Laura Locatelli Alessandra Cazzaniga Giorgia Fedele Monica Zocchi Roberta Scrimieri Claudia Moscheni Sara Castiglioni Jeanette A. Maier |
| author_facet | Laura Locatelli Alessandra Cazzaniga Giorgia Fedele Monica Zocchi Roberta Scrimieri Claudia Moscheni Sara Castiglioni Jeanette A. Maier |
| author_sort | Laura Locatelli |
| collection | DOAJ |
| description | Chemoresistance causes cancer relapse and metastasis, thus remaining the major obstacle to cancer therapy. While some light has been shed on the underlying mechanisms, it is clear that chemoresistance is a multifaceted problem strictly interconnected with the high heterogeneity of neoplastic cells. We utilized two different human cell lines, i.e., LoVo colon cancer and promyelocytic leukemia HL60 cells sensitive and resistant to doxorubicin (DXR), largely used as a chemotherapeutic and frequently leading to chemoresistance. LoVo and HL60 resistant cells accumulate less reactive oxygen species by differently modulating the levels of some pro- and antioxidant proteins. Moreover, the content of intracellular magnesium, known to contribute to protect cells from oxidative stress, is increased in DXR-resistant LoVo through the upregulation of MagT1 and in DXR-resistant HL60 because of the overexpression of TRPM7. In addition, while no major differences in mitochondrial mass are observed in resistant HL60 and LoVo cells, fragmented mitochondria due to increased fission and decreased fusion are detected only in resistant LoVo cells. We conclude that DXR-resistant cells evolve adaptive mechanisms to survive DXR cytotoxicity by activating different molecular pathways. |
| first_indexed | 2024-03-10T08:15:00Z |
| format | Article |
| id | doaj.art-c3f20f14080e4f1db646baa801dd90df |
| institution | Directory Open Access Journal |
| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-10T08:15:00Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj.art-c3f20f14080e4f1db646baa801dd90df2023-11-22T10:28:30ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452021-05-0143116317510.3390/cimb43010014A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying MechanismsLaura Locatelli0Alessandra Cazzaniga1Giorgia Fedele2Monica Zocchi3Roberta Scrimieri4Claudia Moscheni5Sara Castiglioni6Jeanette A. Maier7Department of Biomedical and Clinical Sciences L. Sacco, Università di Milano, Via G.B. Grassi 74, 20157 Milano, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, Università di Milano, Via G.B. Grassi 74, 20157 Milano, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, Università di Milano, Via G.B. Grassi 74, 20157 Milano, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, Università di Milano, Via G.B. Grassi 74, 20157 Milano, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, Università di Milano, Via G.B. Grassi 74, 20157 Milano, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, Università di Milano, Via G.B. Grassi 74, 20157 Milano, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, Università di Milano, Via G.B. Grassi 74, 20157 Milano, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, Università di Milano, Via G.B. Grassi 74, 20157 Milano, ItalyChemoresistance causes cancer relapse and metastasis, thus remaining the major obstacle to cancer therapy. While some light has been shed on the underlying mechanisms, it is clear that chemoresistance is a multifaceted problem strictly interconnected with the high heterogeneity of neoplastic cells. We utilized two different human cell lines, i.e., LoVo colon cancer and promyelocytic leukemia HL60 cells sensitive and resistant to doxorubicin (DXR), largely used as a chemotherapeutic and frequently leading to chemoresistance. LoVo and HL60 resistant cells accumulate less reactive oxygen species by differently modulating the levels of some pro- and antioxidant proteins. Moreover, the content of intracellular magnesium, known to contribute to protect cells from oxidative stress, is increased in DXR-resistant LoVo through the upregulation of MagT1 and in DXR-resistant HL60 because of the overexpression of TRPM7. In addition, while no major differences in mitochondrial mass are observed in resistant HL60 and LoVo cells, fragmented mitochondria due to increased fission and decreased fusion are detected only in resistant LoVo cells. We conclude that DXR-resistant cells evolve adaptive mechanisms to survive DXR cytotoxicity by activating different molecular pathways.https://www.mdpi.com/1467-3045/43/1/14doxorubicinLoVo cellsHL60 cellsTRPM7MagT1ROS |
| spellingShingle | Laura Locatelli Alessandra Cazzaniga Giorgia Fedele Monica Zocchi Roberta Scrimieri Claudia Moscheni Sara Castiglioni Jeanette A. Maier A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying Mechanisms Current Issues in Molecular Biology doxorubicin LoVo cells HL60 cells TRPM7 MagT1 ROS |
| title | A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying Mechanisms |
| title_full | A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying Mechanisms |
| title_fullStr | A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying Mechanisms |
| title_full_unstemmed | A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying Mechanisms |
| title_short | A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying Mechanisms |
| title_sort | comparison of doxorubicin resistant colon cancer lovo and leukemia hl60 cells common features different underlying mechanisms |
| topic | doxorubicin LoVo cells HL60 cells TRPM7 MagT1 ROS |
| url | https://www.mdpi.com/1467-3045/43/1/14 |
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