Monitoring the action of redox-directed cancer therapeutics using a human peroxiredoxin-2-based probe
Redox cancer therapeutics target the increased reliance on intracellular antioxidant systems and enhanced susceptibility to oxidant-induced stress of some cancer cells compared to normal cells. Many of these therapeutics are thought to perturb intracellular levels of the oxidant hydrogen peroxide (H...
Main Authors: | , , , , |
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Other Authors: | |
Format: | Article |
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Nature Publishing Group
2019
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Online Access: | http://hdl.handle.net/1721.1/120784 https://orcid.org/0000-0002-6003-681X https://orcid.org/0000-0002-9238-8932 https://orcid.org/0000-0002-7096-138X |
Summary: | Redox cancer therapeutics target the increased reliance on intracellular antioxidant systems and enhanced susceptibility to oxidant-induced stress of some cancer cells compared to normal cells. Many of these therapeutics are thought to perturb intracellular levels of the oxidant hydrogen peroxide (H[subscript 2]O[subscript 2]), a signaling molecule that modulates a number of different processes in human cells. However, fluorescent probes for this species remain limited in their ability to detect the small perturbations induced during successful treatments. We report a fluorescent sensor based upon human peroxiredoxin-2, which acts as the natural indicator of small H[subscript 2]O[subscript 2] fluctuations in human cells. The new probe reveals peroxide-induced oxidation in human cells below the detection limit of current probes, as well as peroxiredoxin-2 oxidation caused by two different redox cancer therapeutics in living cells. This capability will be useful in elucidating the mechanism of current redox-based therapeutics and in developing new ones. |
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