HA14-1 is Able to Reconstitute the Impaired Mitochondrial Pathway of Apoptosis in Renal Cell Carcinoma Cell Lines
Renal cell carcinomas (RCCs) exhibit a marked resistance towards apoptosis. Although most apoptotic stimuli converge at the level of the mitochondria, little is known about the mitochondrial apoptosis pathway in renal cell carcinomas. The aim of the present study, therefore, was to investigate the f...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2008-01-01
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| Series: | Cellular Oncology |
| Online Access: | http://dx.doi.org/10.3233/CLO-2008-0438 |
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| _version_ | 1832549436212903936 |
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| author | Sebastian Heikaus Linda van den Berg Tobias Kempf Csaba Mahotka Helmut Erich Gabbert Uwe Ramp |
| author_facet | Sebastian Heikaus Linda van den Berg Tobias Kempf Csaba Mahotka Helmut Erich Gabbert Uwe Ramp |
| author_sort | Sebastian Heikaus |
| collection | DOAJ |
| description | Renal cell carcinomas (RCCs) exhibit a marked resistance towards apoptosis. Although most apoptotic stimuli converge at the level of the mitochondria, little is known about the mitochondrial apoptosis pathway in renal cell carcinomas. The aim of the present study, therefore, was to investigate the functionality of the mitochondrial apoptosis pathway in renal cell carcinoma cell lines by exposure to TRAIL, etoposide, HA14-1 and betulinic acid activating the mitochondria by different mechanisms. Sensitivity to TRAIL-induced apoptosis correlated with cleavage of the initiator caspase-8, but the mitochondrial apoptosis pathway was not induced. Similarly, etoposide and betulinic acid could not induce mitochondrial damage. In contrast, HA14-1 was able to activate mitochondrial apoptosis, thereby demonstrating functionally inducible signalling pathways downstream of the mitochondria. The intactness of the pathways upstream of the mitochondria was shown by pretreatment of TRAIL-sensitive cell lines with HA14-1, which could reconstitute TRAIL-induced mitochondrial damage and resulted in a synergistic apoptosis induction. |
| format | Article |
| id | doaj-art-4a8d5d0e03bc458fa719a3165b21c867 |
| institution | Kabale University |
| issn | 1570-5870 1875-8606 |
| language | English |
| publishDate | 2008-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cellular Oncology |
| spelling | doaj-art-4a8d5d0e03bc458fa719a3165b21c8672025-02-03T06:11:16ZengWileyCellular Oncology1570-58701875-86062008-01-0130541943310.3233/CLO-2008-0438HA14-1 is Able to Reconstitute the Impaired Mitochondrial Pathway of Apoptosis in Renal Cell Carcinoma Cell LinesSebastian Heikaus0Linda van den Berg1Tobias Kempf2Csaba Mahotka3Helmut Erich Gabbert4Uwe Ramp5Institute of Pathology, Heinrich-Heine-University Hospital, 40225 Düsseldorf, GermanyInstitute of Pathology, Heinrich-Heine-University Hospital, 40225 Düsseldorf, GermanyInstitute of Pathology, Heinrich-Heine-University Hospital, 40225 Düsseldorf, GermanyInstitute of Pathology, Heinrich-Heine-University Hospital, 40225 Düsseldorf, GermanyInstitute of Pathology, Heinrich-Heine-University Hospital, 40225 Düsseldorf, GermanyInstitute of Pathology, Heinrich-Heine-University Hospital, 40225 Düsseldorf, GermanyRenal cell carcinomas (RCCs) exhibit a marked resistance towards apoptosis. Although most apoptotic stimuli converge at the level of the mitochondria, little is known about the mitochondrial apoptosis pathway in renal cell carcinomas. The aim of the present study, therefore, was to investigate the functionality of the mitochondrial apoptosis pathway in renal cell carcinoma cell lines by exposure to TRAIL, etoposide, HA14-1 and betulinic acid activating the mitochondria by different mechanisms. Sensitivity to TRAIL-induced apoptosis correlated with cleavage of the initiator caspase-8, but the mitochondrial apoptosis pathway was not induced. Similarly, etoposide and betulinic acid could not induce mitochondrial damage. In contrast, HA14-1 was able to activate mitochondrial apoptosis, thereby demonstrating functionally inducible signalling pathways downstream of the mitochondria. The intactness of the pathways upstream of the mitochondria was shown by pretreatment of TRAIL-sensitive cell lines with HA14-1, which could reconstitute TRAIL-induced mitochondrial damage and resulted in a synergistic apoptosis induction.http://dx.doi.org/10.3233/CLO-2008-0438 |
| spellingShingle | Sebastian Heikaus Linda van den Berg Tobias Kempf Csaba Mahotka Helmut Erich Gabbert Uwe Ramp HA14-1 is Able to Reconstitute the Impaired Mitochondrial Pathway of Apoptosis in Renal Cell Carcinoma Cell Lines Cellular Oncology |
| title | HA14-1 is Able to Reconstitute the Impaired Mitochondrial Pathway of Apoptosis in Renal Cell Carcinoma Cell Lines |
| title_full | HA14-1 is Able to Reconstitute the Impaired Mitochondrial Pathway of Apoptosis in Renal Cell Carcinoma Cell Lines |
| title_fullStr | HA14-1 is Able to Reconstitute the Impaired Mitochondrial Pathway of Apoptosis in Renal Cell Carcinoma Cell Lines |
| title_full_unstemmed | HA14-1 is Able to Reconstitute the Impaired Mitochondrial Pathway of Apoptosis in Renal Cell Carcinoma Cell Lines |
| title_short | HA14-1 is Able to Reconstitute the Impaired Mitochondrial Pathway of Apoptosis in Renal Cell Carcinoma Cell Lines |
| title_sort | ha14 1 is able to reconstitute the impaired mitochondrial pathway of apoptosis in renal cell carcinoma cell lines |
| url | http://dx.doi.org/10.3233/CLO-2008-0438 |
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