GdVO4:Eu3+ and LaVO4:Eu3+ Nanoparticles Exacerbate Oxidative Stress in L929 Cells: Potential Implications for Cancer Therapy

The therapeutic potential of redox-active nanoscale materials as antioxidant- or reactive oxygen species (ROS)-inducing agents was intensely studied. Herein, we demonstrate that the synthesized and characterized GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles, which have been already shown to have redox-act...

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Published in:International journal of molecular sciences 2024-10, Vol.25 (21), p.11687
Main Authors: Kot, Yuriy, Klochkov, Vladimir, Prokopiuk, Volodymyr, Sedyh, Olha, Tryfonyuk, Liliya, Grygorova, Ganna, Karpenko, Nina, Tomchuk, Oleksandr, Kot, Kateryna, Onishchenko, Anatolii, Yefimova, Svetlana, Tkachenko, Anton
Format: Article
Language:English
Subjects:
Apoptosis
Aqueous solutions
Cancer therapies
Cell death
Cytotoxicity
DNA damage
Ferroptosis
Kinases
Medical research
Metabolism
Mutation
Nanomaterials
Nanoparticles
Nanotechnology
Oxidative stress
Reactive oxygen species
Spectrum analysis
Tumors
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Summary:The therapeutic potential of redox-active nanoscale materials as antioxidant- or reactive oxygen species (ROS)-inducing agents was intensely studied. Herein, we demonstrate that the synthesized and characterized GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles, which have been already shown to have redox-active, anti-inflammatory, antibacterial, and wound healing properties, both in vitro and in vivo, worsen oxidative stress of L929 cells triggered by hydrogen peroxide or tert-butyl hydroperoxide (tBuOOH) at the concentrations that are safe for intact L929 cells. This effect was observed upon internalization of the investigated nanosized materials and is associated with the cleavage of caspase-3 and caspase-9 without recruitment of caspase-8. Such changes in the caspase cascade indicate activation of the intrinsic caspase-9-dependent mitochondrial but not the extrinsic death, receptor-mediated, and caspase-8-dependent apoptotic pathway. The GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticle-induced apoptosis of oxidatively compromised L929 cells is mediated by ROS overgeneration, Ca2+ overload, endoplasmic reticulum stress-associated JNK (c-Jun N-terminal kinase), and DNA damage-inducible transcript 3 (DDIT3). Our findings demonstrate that GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles aggravate the oxidative stress-induced damage to L929 cells, indicating that they might potentially be applied as anti-cancer agents.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms252111687