Academic Journal
Pharmacological targeting of c-FLIPL and Bcl-2 family members promotes apoptosis in CD95L-resistant cells
| العنوان: | Pharmacological targeting of c-FLIPL and Bcl-2 family members promotes apoptosis in CD95L-resistant cells |
|---|---|
| المؤلفون: | König, Corinna, Hillert-Richter, Laura K., Ivanisenko, Nikita V., Ivanisenko, Vladimir A., Lavrik, Inna N. |
| سنة النشر: | 2020 |
| المجموعة: | Share it - Open Access und Forschungsdaten-Repositorium der Hochschulbibliotheken in Sachsen-Anhalt |
| مصطلحات موضوعية: | ddc:610, Pharmacological targeting, Apoptosis, CD95L‑resistant cells |
| الوصف: | The development of efficient combinatorial treatments is one of the key tasks in modern anti-cancer therapies. An apoptotic signal can either be induced by activation of death receptors (DR) (extrinsic pathway) or via the mitochondria (intrinsic pathway). Cancer cells are characterized by deregulation of both pathways. Procaspase-8 activation in extrinsic apoptosis is controlled by c-FLIP proteins. We have recently reported the small molecules FLIPinB/FLIPinBγ targeting c-FLIPL in the caspase-8/c- FLIPL heterodimer. These small molecules enhanced caspase-8 activity in the death-inducing signaling complex (DISC), CD95L/TRAIL-induced caspase-3/7 activation and subsequent apoptosis. In this study to increase the pro-apoptotic effects of FLIPinB/FLIPinBγ and enhance its therapeutic potential we investigated costimulatory effects of FLIPinB/FLIPinBγ in combination with the pharmacological inhibitors of the anti-apoptotic Bcl-2 family members such as ABT-263 and S63845. The combination of these inhibitors together with FLIPinB/FLIPinBγ increased CD95L-induced cell viability loss, caspase activation and apoptosis. Taken together, our study suggests new approaches for the development of combinatorial anti-cancer therapies specifically targeting both intrinsic and extrinsic apoptosis pathways. ; DFG-Publikationsfonds 2020 |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| ردمك: | 978-1-74243-183-3 1-74243-183-6 |
| Relation: | https://www.nature.com/srep/; http://dx.doi.org/10.25673/36472 |
| DOI: | 10.25673/36472 |
| الاتاحة: | https://opendata.uni-halle.de//handle/1981185920/36704 https://doi.org/10.25673/36472 https://nbn-resolving.org/urn:nbn:de:gbv:ma9:1-1981185920-367044 |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.BD0154A8 |
| قاعدة البيانات: | BASE |
| ردمك: | 9781742431833 1742431836 |
|---|---|
| DOI: | 10.25673/36472 |