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...

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Bibliographic Details
Main Authors: Langford, Troy F., Huang, Beijing Kara, Lim, Joseph B., Moon, Sun Jin, Sikes Johnson, Hadley
Other Authors: Massachusetts Institute of Technology. Department of Chemical Engineering
Format: Article
Published: Nature Publishing Group 2019
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
Description
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.