Using Sensors and Generators of H2O2 to Elucidate the Toxicity Mechanism of Piperlongumine and Phenethyl Isothiocyanate

Antioxidants & Redox Signaling
Beijing K HuangHadley D Sikes

Abstract

Chemotherapeutics target vital functions that ensure survival of cancer cells, including their increased reliance on defense mechanisms against oxidative stress compared to normal cells. Many chemotherapeutics exploit this vulnerability to oxidative stress by elevating the levels of intracellular reactive oxygen species (ROS). A quantitative understanding of the oxidants generated and how they induce toxicity will be important for effective implementation and design of future chemotherapeutics. Molecular tools that facilitate measurement and manipulation of individual chemical species within the context of the larger intracellular redox network present a means to develop this understanding. In this work, we demonstrate the use of such tools to elucidate the roles of H2O2 and glutathione (GSH) in the toxicity mechanism of two ROS-based chemotherapeutics, piperlongumine and phenethyl isothiocyanate. Depletion of GSH as a result of treatment with these compounds is not an important part of the toxicity mechanisms of these drugs and does not lead to an increase in the intracellular H2O2 level. Measuring peroxiredoxin-2 (Prx-2) oxidation as evidence of increased H2O2, only piperlongumine treatment shows elevation and it is GSH indep...Continue Reading

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Citations

Jul 4, 2018·Endocrine-related Cancer·James F PowersArthur S Tischler
Oct 12, 2018·Endocrine-related Cancer·James F PowersArthur S Tischler
Oct 27, 2020·Systems Biology in Reproductive Medicine·Jiu-Yuan FuYan-Ju Zhu
Jul 11, 2020·Free Radical Biology & Medicine·Yantao BaoWei-Guo Zhu
Feb 20, 2021·Biosensors & Bioelectronics·Shigekuni HosogiLeonardo Puppulin
Jan 12, 2022·Biochemical Society Transactions·Asal Ghaffari ZakiEmrah Eroglu

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Methods Mentioned

BETA
Flow cytometry
transfection
Profiler

Software Mentioned

ImageJ
Cell Profiler
HyPer

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