title: Increased cytotoxicity of squamous cell carcinoma of the head and neck by combining cisplatin with VP-16 and ciprofloxacin.
abstract: Chemotherapeutic treatment of squamous cell carcinoma (SCC) of the head and neck has been largely ineffective because of tumor cell resistance. This study examined combinations of cisplatin, 4' demethylepipodophyllotoxin ethylidene D-glucoside (VP-16), and ciprofloxacin, a quinolone antibiotic. VP-16 and ciprofloxacin were used in an effort to inhibit DNA repair and increase cytotoxicity. Chemotherapeutic agents often have a direct damaging effect on cellular DNA. Cytotoxicity may be the result of incomplete DNA repair mechanisms; whereas tumor cell resistance to drugs may be due to efficient DNA recovery. A nuclear enzyme especially important to DNA repair and cell growth is topoisomerase II (topo II). Targeted inhibition of topo II by VP-16 and ciprofloxacin may cause increased cisplatin cytotoxicity. SCC cell lines of head and neck origin were treated with a combination of cisplatin, VP-16, and/or ciprofloxacin with cell viability being assessed by the MTT colorimetric assay. Four of five SCC lines examined demonstrated significant augmentation of cisplatin cytotoxicity with the addition of both VP-16 and ciprofloxacin. These in vitro data suggest methods may exist for improving the chemotherapeutic treatment of SCC of the head and neck.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City.
authors.forename: J
authors.initials: J
authors.lastname: Haller
authors.forename: R
authors.initials: R
authors.lastname: Burgess
authors.forename: D
authors.initials: D
authors.lastname: Dawson
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D002939:Ciprofloxacin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D002939:Ciprofloxacin; D005047:Etoposide; D002945:Cisplatin