| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Hagen, Rudolf Schendzielorz, Philipp Froelich, Katrin Kleinsasser, Norbert Scherzed, Agmal Hackenberg, Stephan Ginzkey, Christian Rak, Kristen |
| Description |
Country affiliation: Germany Author Affiliation: Scherzed A ( Department of OtoRhinoLaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, JuliusMaximilianUniversity of Wuerzburg, Wuerzburg D97080, Germany.); Hackenberg S ( Department of OtoRhinoLaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, JuliusMaximilianUniversity of Wuerzburg, Wuerzburg D97080, Germany.); Froelich K ( Department of OtoRhinoLaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, JuliusMaximilianUniversity of Wuerzburg, Wuerzburg D97080, Germany.); Rak K ( Department of OtoRhinoLaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, JuliusMaximilianUniversity of Wuerzburg, Wuerzburg D97080, Germany.); Ginzkey C ( Department of OtoRhinoLaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, JuliusMaximilianUniversity of Wuerzburg, Wuerzburg D97080, Germany.); Hagen R ( Department of OtoRhinoLaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, JuliusMaximilianUniversity of Wuerzburg, Wuerzburg D97080, Germany.); Schendzielorz P ( Department of OtoRhinoLaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, JuliusMaximilianUniversity of Wuerzburg, Wuerzburg D97080, Germany.); Kleinsasser N ( Department of OtoRhinoLaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, JuliusMaximilianUniversity of Wuerzburg, Wuerzburg D97080, Germany.) |
| Abstract |
Surgery, radiation, chemotherapy or a combinations of these are all accepted modalities for the treatment of head and neck squamous cell carcinoma (HNSCC). Despite this, 4060% of patients suffering from HNSCC develop locoregional failure and/or distant metastases. Salinomycin has been demonstrated to be >100fold more effective than paclitaxel at causing cancer stem cell death, therefore, it may offer an important improvement in cancer therapy. However, the toxicity of salinomycin is of concern. A possible solution may be the administration of additive drugs, which reduce the toxicity. By inhibiting the mitochondrial Na+/Ca2+ exchanger using the benzodiazepine derivate, CGP37157 (CGP), a significant reduction in salinomycin neuronal toxicity has been observed. This raises the question of whether CGP also inhibits the tumor toxicity of salinomycin. In the present study, the FaDu and HLaC79 C1 HNSCC cell lines were treated with salinomycin with or without CGP. Comparative viability assessments were performed using microscopy, a fluorescein diacetate assay, an MTT assay, a clonogenic assay and annexin Vpropidium iodide staining. The expression levels of MDR1 were monitored using reverse transcriptionquantitative polymerase chain reaction. Salinomycin alone, and in combination with CGP, achieved a significant attenuation of cell viability and increased apoptosis in a dosedependent manner. However, the tumor toxicity of salinomycin was not inhibited by CGP. The HLaC79 C1 cells were more sensitive to salinomycin, compared with the FaDu cells, with this sensitivity being due to high expression levels of MDR1 by the HLaC79 C1 cells. In conclusion, CGP did not counteract the tumor toxicity of salinomycin in vitro and may be a promising drug in future anticancer therapy. The results of the present study encourages further investigation of the toxicological aspects of salinomycin, particularly in human cells and animal models. |
| ISSN |
17912997 |
| e-ISSN |
17913004 |
| Journal |
Molecular Medicine Reports |
| Issue Number |
3 |
| Volume Number |
12 |
| Language |
English |
| Publisher |
Spandidos Publications |
| Publisher Date |
2015-09-01 |
| Publisher Place |
Greece |
| Access Restriction |
Open |
| Subject Keyword |
Antineoplastic Agents Pharmacology Clonazepam Analogs & Derivatives Pyrans Thiazepines Apoptosis Carcinoma, Squamous Cell Cell Line, Tumor Cell Shape Drug Effects Drug Screening Assays, Antitumor Gene Expression Head And Neck Neoplasms P-glycoproteins Genetics Metabolism Research Support, Non-u.s. Gov't Discipline Molecular Biology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Genetics Biochemistry Molecular Biology Cancer Research Molecular Medicine Oncology |
