Redox status and metabolomic profiling of thioredoxin reductase inhibitors and 4 kGy ionizing radiation-exposed Deinococcus radiodurans

Sudharsan, M.; Prasad, N. N.; Kanimozhi, G.; Rishiikeshwer, B.S.; Brindha, G.; Chakraborty, Anindita

doi:10.1016/j.micres.2022.127070

Cited by 8 publications

(5 citation statements)

References 56 publications

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“…Ten micromoles of Fast‐TRFS was added to the control and auranofin‐treated MDA‐MB‐231 and MCF‐7 cells and incubated for 10 min. Fluorescence intensity was measured in a time‐dependent manner using a multimode reader (Molecular Devices) 32 . Images of cells were taken in a dose‐dependent manner under an fluorescent microscope (Floid Cell Imaging Station, Life Technologies).…”

Section: Methodsmentioning

confidence: 99%

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Auranofin sensitizes breast cancer cells to paclitaxel chemotherapy by disturbing the cellular redox system

Natarajan,

Prasad,

Sudharsan

et al. 2023

Cell Biochemistry & Function

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The intrinsic redox status of cancer cells limits the efficacy of chemotherapeutic drugs. Auranofin, a Food and Drug Administration‐approved gold‐containing compound, documented with effective pharmacokinetics and safety profiles in humans, has recently been repurposed for anticancer activity. This study examined the paclitaxel‐sensitizing effect of auranofin by targeting redox balance in the MDA‐MB‐231 and MCF‐7 breast cancer cell lines. Auranofin treatment depletes the activities of superoxide dismutase, catalase, and glutathione peroxidase and alters the redox ratio in the breast cancer cell lines. Furthermore, it has been noticed that auranofin augmented paclitaxel‐mediated cytotoxicity in a concentration‐dependent manner in both MDA‐MB‐231 and MCF‐7 cell lines. Moreover, auranofin increased the levels of intracellular reactive oxygen species (observed using 2, 7‐diacetyl dichlorofluorescein diacetate staining) and subsequently altered the mitochondrial membrane potential (rhodamine‐123 staining) in a concentration‐dependent manner. Further, the expression of apoptotic marker p21 was found to be higher in auranofin plus paclitaxel‐treated breast cancer cells compared to paclitaxel‐alone treatment. Thus, the present results illustrate the chemosensitizing property of auranofin in MDA‐MB‐231 and MCF‐7 breast cancer cell lines via oxidative metabolism. Therefore, auranofin could be considered a chemosensitizing agent during cancer chemotherapy.

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Section: Methodsmentioning

confidence: 99%

“…Fluorescence intensity was measured in a time-dependent manner using a multimode reader (Molecular Devices). 32 Images of cells were taken in a dose-dependent manner under an fluorescent microscope (Floid Cell Imaging Station, Life Technologies). The excitation and emission wavelengths were 343 and 485 nm, respectively.…”

Section: Fast-trfs Assaymentioning

confidence: 99%

Auranofin sensitizes breast cancer cells to paclitaxel chemotherapy by disturbing the cellular redox system

Natarajan,

Prasad,

Sudharsan

et al. 2023

Cell Biochemistry & Function

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“…Mercury tolerance also involves the Trx system in Thermus thermophilus (Norambuena et al, 2018). Finally, a role in radiation tolerance has been demonstrated in D. radiodurans (Sudharsan et al, 2022). Consistently, the expression of trx genes is controlled by stress exposure in most organisms.…”

Section: The Direct and Indirect Roles Of Trx Systems In Stress‐responsementioning

confidence: 99%

“…Among the different classes of RNRs, class Ia enzymes of L. monocytogenes , E. coli and S. enterica , and class II enzymes of Clostridia, Mycobacteria, S. enterica and D. radiodurans , use Trx systems for reduction. This might partly explain the involvement of Trx systems in tolerance to stresses inducing DNA damage in D. radiodurans (Sudharsan et al, 2022).…”

Section: The Direct and Indirect Roles Of Trx Systems In Stress‐responsementioning

confidence: 99%

From ubiquity to specificity: The diverse functions of bacterial thioredoxin systems

Anjou,

Lotoux,

Morvan

et al. 2024

Environmental Microbiology

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The thioredoxin (Trx) system, found universally, is responsible for the regeneration of reversibly oxidized protein thiols in living cells. This system is made up of a Trx and a Trx reductase, and it plays a central role in maintaining thiol‐based redox homeostasis by reducing oxidized protein thiols, such as disulfide bonds in proteins. Some Trxs also possess a chaperone function that is independent of thiol‐disulfide exchange, in addition to their thiol‐disulfide reductase activity. These two activities of the Trx system are involved in numerous physiological processes in bacteria. This review describes the diverse physiological roles of the Trx system that have emerged throughout bacterial evolution. The Trx system is essential for responding to oxidative and nitrosative stress. Beyond this primary function, the Trx system also participates in redox regulation and signal transduction, and in controlling metabolism, motility, biofilm formation, and virulence. This range of functions has evolved alongside the diversity of bacterial lifestyles and their specific constraints. This evolution can be characterized by the multiplication of the systems and by the specialization of cofactors or targets to adapt to the constraints of atypical lifestyles, such as photosynthesis, insect endosymbiosis, or spore‐forming bacteria.

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“…The alteration of the redox system was associated with cell death of D. radiodurans mediated by hydrogen peroxide-induced oxidative stress. The intracellular redox status was further illustrated by metabolomic and proteomic profiling in response to ebselen and radiation treatment [ 28 , 29 ]. The results revealed a change in the composition and concentration of metabolites [ 28 ] and a decrease in the expression of essential cellular proteins (e.g., those involved in glycolysis, proteases, peptidases, and peptide transporters) that are necessary for the survival of the bacterium with exposure to ionizing radiation [ 29 ].…”

Section: Inhibition Of Bacterial Thioredoxin Reductasementioning

confidence: 99%

Antibacterial Activity of Ebselen

Maślanka

Mucha

2023

IJMS

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Ebselen is a low-molecular-weight organoselenium compound that has been broadly studied for its antioxidant, anti-inflammatory, and cytoprotective properties. These advantageous properties were initially associated with mimicking the activity of selenoprotein glutathione peroxidase, but the biomedical impact of this compound appear to be far more complex. Ebselen serves as a substrate or inhibitor with multiple protein/enzyme targets, whereas inhibition typically originates from the covalent modification of cysteine residues by opening the benzisoselenazolone ring and S–Se bond formation. The inhibition of enzymes of various classes and origins has been associated with substantial antimicrobial potential among other activities. In this contribution, we summarize the current state of the art regarding the antibacterial activity of ebselen. This activity, alone and in combination with commercial pharmaceuticals, against pathogens, including those resistant to drugs, is presented, together with the molecular mechanism behind the reactivity. The specific inactivation of thioredoxin reductase, bacterial toxins, and other resistance factors is considered to have certain therapeutic implications. Synergistic action and sensitization to common antibiotics assisted with the use of ebselen appear to be promising directions in the treatment of persistent infections.

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Redox status and metabolomic profiling of thioredoxin reductase inhibitors and 4 kGy ionizing radiation-exposed Deinococcus radiodurans

Cited by 8 publications

References 56 publications

Auranofin sensitizes breast cancer cells to paclitaxel chemotherapy by disturbing the cellular redox system

Auranofin sensitizes breast cancer cells to paclitaxel chemotherapy by disturbing the cellular redox system

From ubiquity to specificity: The diverse functions of bacterial thioredoxin systems

Antibacterial Activity of Ebselen

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