Mirjam Gerwing1, Christine Jacobsen1, Sergey Dyshlovoy1,2,3, Jessica Hauschild1, Tina Rohlfing1, Christoph Oing1, Simone Venz4,5, Jan Oldenburg6,7, Karin Oechsle1, Carsten Bokemeyer1, Gunhild von Amsberg1, Friedemann Honecker8,9. 1. Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Martinistaße 52, 20246, Hamburg, Germany. 2. Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, Prospect 100 Let Vladivostoku 159, Vladivostok, Russia, 690022. 3. School of Natural Sciences, Far East Federal University, Sukhanova Street 8, Vladivostok, Russia, 690950. 4. Department of Medical Biochemistry and Molecular Biology, University of Greifswald, Fleischmannstraße 42-44, 17475, Greifswald, Germany. 5. Department of Functional Genomics, Interfacultary Institute of Genetics and Functional Genomics, University of Greifswald, Friedrich-Ludwig-Jahn-Straße 15 a, 17487, Greifswald, Germany. 6. Department of Oncology, Akershus, University Hospital, POB 1000, 1478, Lørenskog, Norway. 7. University of Oslo, Blindern, P.O. Box 1072, 0316, Oslo, Norway. 8. Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Martinistaße 52, 20246, Hamburg, Germany. friedemann.honecker@zetup.ch. 9. Tumor and Breast Center ZeTuP, Rorschacher Strasse 150, 9006, St. Gallen, Switzerland. friedemann.honecker@zetup.ch.
Abstract
BACKGROUND: Cisplatin-based chemotherapy is highly effective in metastasized germ cell tumours (GCT). However, 10-30 % of patients develop resistance to cisplatin, requiring salvage therapy. We investigated the in vitro activity of paclitaxel and the novel taxane cabazitaxel in cisplatin-sensitive and -resistant GCT cell lines. METHODS: In vitro activity of paclitaxel and cabazitaxel was determined by proliferation assays, and mode of action of cabazitaxel was assessed by western blotting and two screening approaches, i.e. whole proteome analysis and a human apoptosis array. RESULTS: Activity of paclitaxel and cabazitaxel was not affected by cisplatin resistance, suggesting that there is no cross-resistance between these agents in vitro. Cabazitaxel treatment showed a strong inhibitory effect on colony formation capacity. Cabazitaxel induced classical apoptosis in all cell lines, reflected by cleavage of PARP and caspase 3, without inducing specific changes in the cell cycle distribution. Using the proteomic and human apoptosis array screening approaches, differential regulation of several proteins, including members of the bcl-2 family, was found, giving first insights into the mode of action of cabazitaxel in GCT. CONCLUSION: Cabazitaxel shows promising in vitro activity in GCT cells, independent of levels of cisplatin resistance.
BACKGROUND:Cisplatin-based chemotherapy is highly effective in metastasized germ cell tumours (GCT). However, 10-30 % of patients develop resistance to cisplatin, requiring salvage therapy. We investigated the in vitro activity of paclitaxel and the novel taxane cabazitaxel in cisplatin-sensitive and -resistant GCT cell lines. METHODS: In vitro activity of paclitaxel and cabazitaxel was determined by proliferation assays, and mode of action of cabazitaxel was assessed by western blotting and two screening approaches, i.e. whole proteome analysis and a human apoptosis array. RESULTS: Activity of paclitaxel and cabazitaxel was not affected by cisplatin resistance, suggesting that there is no cross-resistance between these agents in vitro. Cabazitaxel treatment showed a strong inhibitory effect on colony formation capacity. Cabazitaxel induced classical apoptosis in all cell lines, reflected by cleavage of PARP and caspase 3, without inducing specific changes in the cell cycle distribution. Using the proteomic and human apoptosis array screening approaches, differential regulation of several proteins, including members of the bcl-2 family, was found, giving first insights into the mode of action of cabazitaxel in GCT. CONCLUSION:Cabazitaxel shows promising in vitro activity in GCT cells, independent of levels of cisplatin resistance.
Authors: Friedemann Honecker; Tina Rohlfing; Sönke Harder; Melanie Braig; Ad J M Gillis; Stephanie Glaesener; Christine Barett; Carsten Bokemeyer; Friedrich Buck; Tim H Brümmendorf; Leendert H J Looijenga; Stefan Balabanov Journal: J Proteomics Date: 2013-11-22 Impact factor: 4.044
Authors: Christoph Oing; Marcus Hentrich; Anja Lorch; Dietrich Gläser; Holger Rumpold; Sebastian Ochsenreither; Stephan Richter; Annette Dieing; Stefanie Zschäbitz; Ronnie Rodrigues Pereira; Carsten Bokemeyer; Christoph Seidel Journal: J Cancer Res Clin Oncol Date: 2019-12-14 Impact factor: 4.553
Authors: Ratnakar Singh; Zeeshan Fazal; Andrea K Corbet; Emmanuel Bikorimana; Jennifer C Rodriguez; Ema M Khan; Khadeeja Shahid; Sarah J Freemantle; Michael J Spinella Journal: Cancers (Basel) Date: 2019-06-08 Impact factor: 6.639