Analysis of the horseradish peroxidase/indole-3-acetic acid combination in a three-dimensional tumor model |
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Authors: | Tupper Joanna Greco Olga Tozer Gillian M Dachs Gabi U |
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Institution: | Gray Cancer Institute, P.O. Box 100, Mount Vernon Hospital, Northwood, Middlesex, HA6 2JR, UK. |
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Abstract: | 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. |
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