ABSTRACT
A study was performed to improve cytotoxicity determinations by eliminating flavin-mediated photosensitization from tests with KB cells, NCI-H69 cells, P-glycoprotein expressing KBC5-8 cells, MRP1-expressing H69AR cells, and A240286S human lung adenocarcinoma cells. Growth inhibition by cis-platin, doxorubicin, etoposide, gemcitabine, taxol, vincristine, vinblastine, and vinorelbine was determined under flavin-protecting conditions using flavin-free culture media with fetal bovine serum as the only source of flavins. As compared to conventional tests, the IC50 values determined under flavin-protecting conditions reflected increased apparent drug cytotoxicities, and were flawlessly reproducible. Flavin-mediated photosensitization should, therefore, be strictly eliminated from in vitro experiments involving cytotoxic and other drugs.
Subject(s)
Drug Screening Assays, Antitumor/methods , Riboflavin/chemistry , ATP Binding Cassette Transporter, Subfamily B, Member 1/analysis , Cell Proliferation/drug effects , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Humans , KB Cells , Photochemistry , Topoisomerase II InhibitorsABSTRACT
BACKGROUND: Glufosfamide is a novel alkylating agent in which the active metabolite of isophosphoramide mustard is glycosidically linked to beta-D-glucose. Targeting the elevated glucose uptake of tumor cells expressing the SAAT1 glucose transporter, glufosfamide represents an attractive new drug for cancer chemotherapy. The present study investigates the ex vivo responsiveness of Head and Neck Squamous Cell Carcinoma (HNSCC) specimens to glufosfamide. PATIENTS AND METHODS: Twenty-one unselected HNSCC specimens were investigated using a novel ex vivo colony formation assay to determine the epithelial drug response. The individual responsiveness to glufosfamide and to cis-platinum was determined. RESULTS: Five out of 21 evaluable HNSCC specimens were sensitive to glufosfamide. There was a tendency for glufosfamide sensitivity in platinum-resistant specimens and vice versa. CONCLUSION: The effectiveness of glufosfamide observed in the present ex vivo study suggests at least an equipotentiality of glufosfamide in comparison to cis-platinum. The potential clinical usefulness of glufosfamide in HNSCC warrants further evaluation.
