Potential Energy Curve for Singlet-Oxygen Quenching Reaction by Vitamin E

Tasaka, Tomohiko; Matsumoto, Takatoshi; Nagashima, Umpei; Nagaoka, Shin‐ichi

doi:10.2139/ssrn.4352161

Cited by 1 publication

(1 citation statement)

References 25 publications

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“…NAC can also interact directly with ROS and nitrogen species because it is a scavenger of oxygen free radicals 39 . α-tocopherol can significantly scavenge both peroxyl and singlet oxygen species 40,41 , both of which can cause DNA damage 42,43 . Therefore, we used NAC and α-tocopherol as scavengers to remove the DNA damage-inducing ROS that are produced in cells upon inhibition of the Trx system.…”

Section: Ros Does Not Play a Critical Role In Trx1 Kd-induced Rs Or T...mentioning

confidence: 99%

The thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity

Prasad,

Oo,

Liu

et al. 2024

Nat Commun

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Checkpoint kinase 1 (CHK1) is critical for cell survival under replication stress (RS). CHK1 inhibitors (CHK1i’s) in combination with chemotherapy have shown promising results in preclinical studies but have displayed minimal efficacy with substantial toxicity in clinical trials. To explore combinatorial strategies that can overcome these limitations, we perform an unbiased high-throughput screen in a non-small cell lung cancer (NSCLC) cell line and identify thioredoxin1 (Trx1), a major component of the mammalian antioxidant-system, as a determinant of CHK1i sensitivity. We establish a role for redox recycling of RRM1, the larger subunit of ribonucleotide reductase (RNR), and a depletion of the deoxynucleotide pool in this Trx1-mediated CHK1i sensitivity. Further, the TrxR inhibitor auranofin, an approved anti-rheumatoid arthritis drug, shows a synergistic interaction with CHK1i via interruption of the deoxynucleotide pool. Together, we show a pharmacological combination to treat NSCLC that relies on a redox regulatory link between the Trx system and mammalian RNR activity.

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