title: Effects of salinomycin and CGP37157 on head and neck squamous cell carcinoma cell lines in vitro.
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, 40‑60% of patients suffering from HNSCC develop loco‑regional failure and/or distant metastases. Salinomycin has been demonstrated to be >100‑fold 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 V‑propidium iodide staining. The expression levels of MDR‑1 were monitored using reverse transcription‑quantitative polymerase chain reaction. Salinomycin alone, and in combination with CGP, achieved a significant attenuation of cell viability and increased apoptosis in a dose‑dependent 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 MDR‑1 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.
authors.affiliation: Department of Oto‑Rhino‑Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Julius‑Maximilian‑University of Wuerzburg, Wuerzburg D‑97080, Germany.
authors.forename: Agmal
authors.initials: A
authors.lastname: Scherzed
authors.affiliation: Department of Oto‑Rhino‑Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Julius‑Maximilian‑University of Wuerzburg, Wuerzburg D‑97080, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hackenberg
authors.affiliation: Department of Oto‑Rhino‑Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Julius‑Maximilian‑University of Wuerzburg, Wuerzburg D‑97080, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Froelich
authors.affiliation: Department of Oto‑Rhino‑Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Julius‑Maximilian‑University of Wuerzburg, Wuerzburg D‑97080, Germany.
authors.forename: Kristen
authors.initials: K
authors.lastname: Rak
authors.affiliation: Department of Oto‑Rhino‑Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Julius‑Maximilian‑University of Wuerzburg, Wuerzburg D‑97080, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ginzkey
authors.affiliation: Department of Oto‑Rhino‑Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Julius‑Maximilian‑University of Wuerzburg, Wuerzburg D‑97080, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hagen
authors.affiliation: Department of Oto‑Rhino‑Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Julius‑Maximilian‑University of Wuerzburg, Wuerzburg D‑97080, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schendzielorz
authors.affiliation: Department of Oto‑Rhino‑Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Julius‑Maximilian‑University of Wuerzburg, Wuerzburg D‑97080, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Kleinsasser
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002998:Clonazepam / Q000031:analogs & derivatives* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D015870:Gene Expression; D006258:Head and Neck Neoplasms; D006801:Humans; D011714:Pyrans / Q000494:pharmacology*; D013841:Thiazepines / Q000494:pharmacology*; D000095662:Polyether Polyketides
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D002998:Clonazepam; D011714:Pyrans; D013841:Thiazepines; C513055:ABCB1 protein, human; C010327:salinomycin; D000095662:Polyether Polyketides; C079032:CGP 37157