Analysis of the horseradish peroxidase/indole-3-acetic acid combination in a three-dimensional tumor model.
Horseradish peroxidase has previously been shown to catalyze the conversion of indole-3-acetic acid (IAA) to a potent cytotoxin in a gene therapy setting. A three-dimensional spheroid model composed of a human head and neck carcinoma cell line, has been used to mimic the tumor microenvironment, such as regions of hypoxia. Exposure of intact spheroids to 0.05-5 mM concentrations of IAA and the halogenated indole, 5-bromoindole-3-acetic acid (5Br-IAA), resulted in decreased cell survival, and demonstrates that this combination is effective under tumor-simulated conditions. In addition, 5Br-IAA, displayed selectivity for spheroids with a large hypoxic fraction following short exposure times.
Tupper
Joanna
J
Gray Cancer Institute, P.O. Box 100, Mount Vernon Hospital, Northwood, Middlesex, HA6 2JR, UK.
Greco
Olga
O
Tozer
Gillian M
GM
Dachs
Gabi U
GU
D018929:Cell Culture Techniques; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D006735:Horseradish Peroxidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007210:Indoleacetic Acids / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D008954:Models, Biological; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D007210:Indoleacetic Acids; C030737:indoleacetic acid; D006735:Horseradish Peroxidase