Possible use of indole-3-acetic acid and its antagonist tryptophan betaine in controlled killing of horseradish peroxidase-labeled human cells

It has been proposed that combination of indole-3-acetic acid (IAA) and horseradish peroxidase (HRP) could be useful as the basis for targeted cancer therapy involving antibody-, polymer-, or gene-directed approaches. By circulating IAA in human body, the cells labeled with HRP could be selectively killed since cytotoxic radical species are produced by IAA-HRP reaction. To enable the finely geared controls in selective killing of the cells, the author propose the use of a fungal alkaloid, hypaphorine known to act against IAA in growing plants, in combination with IAA. Previously, the author and colleagues have shown that hypaphorine competitively inhibits the IAA-dependent superoxide generation by HRP. Since hypaphorine is structurally similar to IAA, the effects of hypaphorine against IAA may be due to competitive binding to the IAA-binding domain on HRP. Our in vitro studies on hypaphorine-based control of the IAA-HRP reaction yielding superoxide, must be re-examined in in vivo systems prior to clinical examination. (C) 2003 Elsevier Science Ltd. All rights reserved.