Cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: Comparison with osteosarcoma cells
Objective Doxorubicin (Dox) is a frontline chemotherapeutic against osteosarcoma (OS) that is plagued by side effects, particularly in the heart. The specific objective of this article is to investigate whether low-dose Dox treatment had pro-autophagic effects in cardiomyocytes as well as osteosarco...
| Main Authors: | , , , , , |
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| Format: | Journal Article |
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Blackwell Publishing Ltd
2015
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| Online Access: | http://hdl.handle.net/20.500.11937/11838 |
| _version_ | 1848747912404664320 |
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| author | Tacar, O. Indumathy, S. Tan, M. Baindur-Hudson, S. Friedhuber, A. Dass, Crispin |
| author_facet | Tacar, O. Indumathy, S. Tan, M. Baindur-Hudson, S. Friedhuber, A. Dass, Crispin |
| author_sort | Tacar, O. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Objective Doxorubicin (Dox) is a frontline chemotherapeutic against osteosarcoma (OS) that is plagued by side effects, particularly in the heart. The specific objective of this article is to investigate whether low-dose Dox treatment had pro-autophagic effects in cardiomyocytes as well as osteosarcoma cells. Methods This study characterises apoptotic (Bax) and autophagic (Beclin-1) biomarker levels in human OS and cardiomyocyte cell lines as well as in various tissues when mice are exposed to low (1-mg/kg, thrice weekly) and high (3-mg/kg thrice weekly) dose Dox for a month. Key findings There was a decrease in Bax and increase in Beclin-1 in cardiac tissue in the high-dose group. Dox decreased Beclin-1 in the skin and liver, with no clear indication in the stomach, small intestine and testis. At low Dox doses of 10 and 100-nm in cardiomyocytes and OS cells, there is a pro-apoptotic effect, with a quicker response in the 100-nm condition, and a slower but steady increase of a pro-apoptotic response at the lower 10-nm dose. However, electron microscopy images revealed changes to human OS cells that resembled autophagy. Human prostate, breast and colorectal cells treated with 10-nm Dox showed ~ 40% reduction in cell viability after 24-h. Conclusion In culture, cells of both cardiomyocytes and OS revealed a predominant pro-apoptotic response at the expense of autophagy, although both seemed to be occurring in vivo. |
| first_indexed | 2025-11-14T06:56:41Z |
| format | Journal Article |
| id | curtin-20.500.11937-11838 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:56:41Z |
| publishDate | 2015 |
| publisher | Blackwell Publishing Ltd |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-118382017-09-13T14:56:20Z Cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: Comparison with osteosarcoma cells Tacar, O. Indumathy, S. Tan, M. Baindur-Hudson, S. Friedhuber, A. Dass, Crispin Objective Doxorubicin (Dox) is a frontline chemotherapeutic against osteosarcoma (OS) that is plagued by side effects, particularly in the heart. The specific objective of this article is to investigate whether low-dose Dox treatment had pro-autophagic effects in cardiomyocytes as well as osteosarcoma cells. Methods This study characterises apoptotic (Bax) and autophagic (Beclin-1) biomarker levels in human OS and cardiomyocyte cell lines as well as in various tissues when mice are exposed to low (1-mg/kg, thrice weekly) and high (3-mg/kg thrice weekly) dose Dox for a month. Key findings There was a decrease in Bax and increase in Beclin-1 in cardiac tissue in the high-dose group. Dox decreased Beclin-1 in the skin and liver, with no clear indication in the stomach, small intestine and testis. At low Dox doses of 10 and 100-nm in cardiomyocytes and OS cells, there is a pro-apoptotic effect, with a quicker response in the 100-nm condition, and a slower but steady increase of a pro-apoptotic response at the lower 10-nm dose. However, electron microscopy images revealed changes to human OS cells that resembled autophagy. Human prostate, breast and colorectal cells treated with 10-nm Dox showed ~ 40% reduction in cell viability after 24-h. Conclusion In culture, cells of both cardiomyocytes and OS revealed a predominant pro-apoptotic response at the expense of autophagy, although both seemed to be occurring in vivo. 2015 Journal Article http://hdl.handle.net/20.500.11937/11838 10.1111/jphp.12324 Blackwell Publishing Ltd restricted |
| spellingShingle | Tacar, O. Indumathy, S. Tan, M. Baindur-Hudson, S. Friedhuber, A. Dass, Crispin Cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: Comparison with osteosarcoma cells |
| title | Cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: Comparison with osteosarcoma cells |
| title_full | Cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: Comparison with osteosarcoma cells |
| title_fullStr | Cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: Comparison with osteosarcoma cells |
| title_full_unstemmed | Cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: Comparison with osteosarcoma cells |
| title_short | Cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: Comparison with osteosarcoma cells |
| title_sort | cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: comparison with osteosarcoma cells |
| url | http://hdl.handle.net/20.500.11937/11838 |