دورية أكاديمية
The BH3 mimetic (±) gossypol induces ROS-independent apoptosis and mitochondrial dysfunction in human A375 melanoma cells in vitro
| العنوان: | The BH3 mimetic (±) gossypol induces ROS-independent apoptosis and mitochondrial dysfunction in human A375 melanoma cells in vitro |
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| المؤلفون: | Kondadi, Arun Kumar, Tsigaras, Thanos, von Montfort, Claudia, Graf, Peter, Stahl, Wilhelm, Brenneisen, Peter |
| المصدر: | http://lobid.org/resources/99370671250806441Test#!, 95(4):1349-1365. |
| سنة النشر: | 2021 |
| المجموعة: | Publisso (ZB MED-Publikationsportal Lebenswissenschaften) |
| مصطلحات موضوعية: | Cell Line, Tumor [MeSH], Membrane Potential, Mitochondrial/drug effects [MeSH], Molecular Toxicology, Humans [MeSH], Reactive Oxygen Species/metabolism [MeSH], Apoptosis/drug effects [MeSH], Apoptosis, Skin Neoplasms/drug therapy [MeSH], Mitochondrial dysfunction, Skin Neoplasms/pathology [MeSH], ROS, Gossypol/pharmacology [MeSH], Cell Death/drug effects [MeSH], Gossypol, Malignant melanoma, Mitochondria/drug effects [MeSH], Antineoplastic Agents, Phytogenic/pharmacology [MeSH], Melanoma/pathology [MeSH], Phytogenic/toxicity [MeSH], Melanoma/drug therapy [MeSH], Gossypol/toxicity [MeSH] |
| الوصف: | A major challenge in current cancer therapy is still the treatment of metastatic melanomas of the skin. BH3 mimetics represent a novel group of substances inducing apoptosis. In this study, we investigated the cytotoxic effect of (±) gossypol (GP), a natural compound from cotton seed, on A375 melanoma cells and the underlying biochemical mechanisms. To prevent undesired side effects due to toxicity on normal (healthy) cells, concentrations only toxic for tumor cells have been elaborated. Viability assays were performed to determine the cytotoxicity of GP in A375 melanoma and normal (healthy) cells. For the majority of experiments, a concentration of 2.5 µM GP was used resulting in a ROS-independent but caspase-dependent cell death of A375 melanoma cells. At this level, GP was non-toxic for normal human epidermal melanocytes. GP has a very short half-life, however, it was demonstrated that only the 'parent' compound and not decomposition products are responsible for the cytotoxic effect in A375 melanoma cells. GP significantly decreased mitochondrial membrane potential accompanied by a Drp1-dependent loss of mitochondrial integrity (fragmentation) in tumor cells. Taken together, GP induced a ROS-independent intrinsic apoptosis leading to the conclusion that within a specific concentration range, GP may work as effective anticancer drug without harmful side effects. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://repository.publisso.de/resource/frl:6451707Test; https://doi.org/10.1007/s00204-021-02987-4Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032633Test/ |
| DOI: | 10.1007/s00204-021-02987-4 |
| الإتاحة: | https://doi.org/10.1007/s00204-021-02987-4Test https://repository.publisso.de/resource/frl:6451707Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032633Test/ |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.50B68ED2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s00204-021-02987-4 |
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