Peroxidase-catalyzed effects of indole-3-acetic acid and analogues on lipid membranes, DNA, and mammalian cells in vitro

Folkes, Lisa K.; Dennis, Madeleine F.; Stratford, Michael R.L.; Candeias, Luis P.; Wardman, Peter

doi:10.1016/s0006-2952(98)00323-2

Cited by 58 publications

(44 citation statements)

References 35 publications

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“…4 The HRP/IAA system is capable of reducing glutathione levels, 7 and inducing DNA strand breaks. 8,9 IAA was able to selectively sensitize HRP-expressing human bladder carcinoma cells to the effects of radiation. 10 Importantly, IAA was able to increase sensitivity under anoxic conditions, in which radical fixation is less likely to occur.…”

Section: Introductionmentioning

confidence: 99%

In vivo characterization of horseradish peroxidase with indole-3-acetic acid and 5-bromoindole-3-acetic acid for gene therapy of cancer

et al. 2010

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Gene-directed enzyme prodrug therapy is a form of targeted cancer therapy, in which an enzyme is used to convert a non-toxic prodrug to a cytotoxin within the tumor. Horseradish peroxidase (HRP) is able to convert the indole prodrugs indole-3-acetic acid (IAA) and the halogenated derivative 5-bromo-IAA (5Br-IAA) to toxic agents able to induce cell kill in vitro. This study characterized HRP-directed gene therapy in vivo. Human nasopharyngeal squamous cell carcinoma cells, FaDu, stably expressing HRP were grown as xenografts in SCID mice. Pharmacokinetic analysis of IAA and 5Br-IAA showed satisfactory drug profiles, and millimolar concentrations could be achieved in tumor tissue at non-toxic doses. HRP-expressing tumors showed a modest growth delay when treated with IAA compared with drug-vehicle controls. Treatment response could not be improved using different drug scheduling or drug vehicle, nor by combining HRP-directed gene therapy with fractionated radiotherapy.

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Section: Introductionmentioning

confidence: 99%

In vivo characterization of horseradish peroxidase with indole-3-acetic acid and 5-bromoindole-3-acetic acid for gene therapy of cancer

et al. 2010

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“…The combination of IAA and horseradish peroxidase is cytotoxic towards mammalian cells. 13 The toxic effect of indole acetic acid in leukocytes is associated with peroxidase activities 14 and these processes have been implicated in activation of glucose and glutamine metabolism. 15 On the other hand, Cano et al showed that the antioxidant effect produced by IAA, in absence of horseradish peroxidase, in vitro is almost so high as that of other indolic compounds.…”

Section: Introductionmentioning

confidence: 99%

Influence of indole acetic acid on antioxidant levels and enzyme activities of glucose metabolism in rat liver

Oliveira

Pugine

Ferreira

et al. 2005

Cell Biochemistry & Function

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Indole acetic acid (IAA) is an auxin and can be synthesized in animals. This compound is metabolized in vitro by peroxidase, producing reactive oxygen species. The toxic effect of indole acetic acid in leukocytes is associated with peroxidase activities and these processes have been implicated in activation of glucose and glutamine metabolism. However, studies in vitro have shown that IAA, in absence of peroxidase, is an antioxidant almost as high in potency as those of other indolic compounds. The purpose of this study was to investigate the possible involvement of a toxic effect of indole acetic acid in the liver, as evidenced by oxidative stress and enzyme activities of the glucose pathway. The animals received IAA by subcutaneous or gavage administration in a phosphate buffered saline (the control group received only the phosphate buffered saline). The other groups received IAA at concentrations of 1 mg, 18 mg and 40 mg per kg of body mass per day. Treatments with 18 mg and 40 mg IAA decreased the activity of catalase by both subcutaneous (30% and 26%) or gavage administration (19% and 28%), respectively. A similar effect was observed on the activity of glutathione peroxidase of animals exposed to 18 mg and 40 mg IAA: A decrease of 34% and 29%, respectively, for subcutaneous administration and a decrease of 29% and 25%, respectively, for gavage administration. However, in neither source of administration did the acid alter superoxide dismutase, glutathione reductase and myeloperoxidase activities. Another alteration was observed in respect of reduced glutathione content in this organ. The lipid peroxidation level showed a significant decrease with subcutaneous (30%, 29% and 24%) and gavage administration (25%, 26% and 24%) using 1 mg, 18 mg and 40 mg of IAA, respectively compared with the control. The reduced glutathione content and catalase activity in the plasma were not altered by either of the two methods of administration. In addition to these findings, after subcutaneous or gavage administration of IAA, the activities of hepatic enzymes of glucose metabolism were not affected (glucokinase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase and citrate synthase). Evidence is presented herein that IAA did not have a pro-oxidant effect in the liver as deduced from a reduction of catalase and glutathione peroxidase activities, a decrease of lipid peroxidation content and no alteration of the pool of reduced glutathione. The effects of IAA were independent of the way of administration.

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“…6,15,16) Moreover, other radicals, such as indolyl, skatolyl, and peroxyl radicals, may be involved in IAA/HRP-induced apoptosis. 17,18) We also propose that H 2 O 2 is a major mediator of IAA/HRP-induced apoptotic cell death. 6) On the other hand, we recently reported that UVB-activated IAA induced apoptotic cell death of cancer cells.…”

Section: Discussionmentioning

confidence: 84%

Experimental Photodynamic Therapy for Liver Cancer Cell-Implanted Nude Mice by an Indole-3-acetic Acid and Intense Pulsed Light Combination

Park

Kim

2009

Biological & Pharmaceutical Bulletin

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Peroxidase-catalyzed effects of indole-3-acetic acid and analogues on lipid membranes, DNA, and mammalian cells in vitro

Cited by 58 publications

References 35 publications

In vivo characterization of horseradish peroxidase with indole-3-acetic acid and 5-bromoindole-3-acetic acid for gene therapy of cancer

In vivo characterization of horseradish peroxidase with indole-3-acetic acid and 5-bromoindole-3-acetic acid for gene therapy of cancer

Influence of indole acetic acid on antioxidant levels and enzyme activities of glucose metabolism in rat liver

Experimental Photodynamic Therapy for Liver Cancer Cell-Implanted Nude Mice by an Indole-3-acetic Acid and Intense Pulsed Light Combination

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