Drug resistance towards etoposide and cisplatin in human melanoma cells is associated with drug-dependent apoptosis deficiency
Anticancer drugs kill susceptible cells through induction of apoptosis. Alterations of apoptotic pathways in drug-resistant tumor cells leading to apoptosis deficiency might represent a potent mechanism conferring drug resistance. We have assessed the effect of etoposide and cisplatin on the apoptot...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
8 December 2015
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| In: |
The journal of investigative dermatology
Year: 2002, Volume: 118, Issue: 6, Pages: 923-932 |
| ISSN: | 1523-1747 |
| DOI: | 10.1046/j.1523-1747.2002.01786.x |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1046/j.1523-1747.2002.01786.x Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0022202X15416707 
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| Author Notes: | Heike Helmbach, Monika A. Kern, Evelyn Rossmann, Kristina Renz, Christine Kissel, Brigitte Gschwendt, and Dirk Schadendorf |
| Summary: | Anticancer drugs kill susceptible cells through induction of apoptosis. Alterations of apoptotic pathways in drug-resistant tumor cells leading to apoptosis deficiency might represent a potent mechanism conferring drug resistance. We have assessed the effect of etoposide and cisplatin on the apoptotic pathways of the drug-sensitive human melanoma cell line MeWo as well as its etoposide- and cisplatin-resistant sublines (MeWoEto01, MeWoEto1, and MeWoCis01, MeWoCis1). Etoposide and cisplatin induced apoptosis in drug-sensitive MeWo cells as indicated by dose-dependent (i) cytochrome c release, (ii) caspase activation, (iii) DNA fragmentation, and (iv) cleavage of poly(ADP-ribose)polymerase. In contrast, whereas low etoposide-resistant cells (MeWoEto01) demonstrated reduced but detectable apoptotic activities, highly etoposide-resistant cells (MeWoEto1) did not exhibit any of the apoptotic events observed in etoposide-induced cell death downstream of a strongly reduced cytochrome c release. Highly cisplatin-resistant cells (MeWoCis1), however, demonstrated a reduced caspase 9 activity and cytochrome c release but the extent of effector caspase activation as well as DNA fragmentation was comparable to that of sensitive MeWo cells at equitoxic concentrations. In addition, poly(ADP-ribose)polymerase cleavage was strongly reduced in highly cisplatin-resistant sublines. Taken together, sensitive and drug-resistant MeWo cells utilized different apoptotic pathways upon drug exposure in a drug-dependent fashion and apoptosis deficiency was strongly associated with the drug-resistant phenotype. |
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| Item Description: | Elektronische Reproduktion der Druckausgabe Gesehen am 11.11.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1523-1747 |
| DOI: | 10.1046/j.1523-1747.2002.01786.x |