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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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
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author Langford, Troy F.
Huang, Beijing Kara
Lim, Joseph B.
Moon, Sun Jin
Sikes Johnson, Hadley
author2 Massachusetts Institute of Technology. Department of Chemical Engineering
author_facet Massachusetts Institute of Technology. Department of Chemical Engineering
Langford, Troy F.
Huang, Beijing Kara
Lim, Joseph B.
Moon, Sun Jin
Sikes Johnson, Hadley
author_sort Langford, Troy F.
collection MIT
description 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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spelling mit-1721.1/1207842022-09-30T09:48:59Z Monitoring the action of redox-directed cancer therapeutics using a human peroxiredoxin-2-based probe Langford, Troy F. Huang, Beijing Kara Lim, Joseph B. Moon, Sun Jin Sikes Johnson, Hadley Massachusetts Institute of Technology. Department of Chemical Engineering Langford, Troy F. Huang, Beijing Kara Lim, Joseph B. Moon, Sun Jin Sikes Johnson, Hadley 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. National Science Foundation (U.S.). Graduate Research Fellowship Program Samsung Fellowship Massachusetts Institute of Technology (Haas Family Fellowship in Chemical Engineering) 2019-03-07T15:08:40Z 2019-03-07T15:08:40Z 2018-08 2019-03-04T14:47:05Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/120784 Langford, Troy F., Beijing K. Huang, Joseph B. Lim, Sun Jin Moon, and Hadley D. Sikes. “Monitoring the Action of Redox-Directed Cancer Therapeutics Using a Human Peroxiredoxin-2-Based Probe.” Nature Communications 9, no. 1 (August 7, 2018). © 2018 The Authors https://orcid.org/0000-0002-6003-681X https://orcid.org/0000-0002-9238-8932 https://orcid.org/0000-0002-7096-138X http://dx.doi.org/10.1038/s41467-018-05557-y Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature
spellingShingle Langford, Troy F.
Huang, Beijing Kara
Lim, Joseph B.
Moon, Sun Jin
Sikes Johnson, Hadley
Monitoring the action of redox-directed cancer therapeutics using a human peroxiredoxin-2-based probe
title Monitoring the action of redox-directed cancer therapeutics using a human peroxiredoxin-2-based probe
title_full Monitoring the action of redox-directed cancer therapeutics using a human peroxiredoxin-2-based probe
title_fullStr Monitoring the action of redox-directed cancer therapeutics using a human peroxiredoxin-2-based probe
title_full_unstemmed Monitoring the action of redox-directed cancer therapeutics using a human peroxiredoxin-2-based probe
title_short Monitoring the action of redox-directed cancer therapeutics using a human peroxiredoxin-2-based probe
title_sort monitoring the action of redox directed cancer therapeutics using a human peroxiredoxin 2 based probe
url 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
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