The involvement of ROS-regulated programmed cell death in hepatocellular carcinoma

Cai, Hanchen; Meng, Ziqi; Yu, Fujun

doi:10.1016/j.critrevonc.2024.104361

Cited by 6 publications

(1 citation statement)

References 170 publications

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“…An extra of MG accumulation enhances ROS production, thereby inducing oxidative stress [32]. This involves the destruction of chemical bonds in biomolecules and leads to the alterations in the structural properties of proteins (enzymes), nucleic acids, and lipids, consequently inducing cellular metabolic dysfunction [33], which is the main trigger for the development of the neurodegenerative disease. As shown in the result (Figure 3), ROS generation increased in PC-12 cells after treatment with MG. An accumulation of ROS leads to mitochondrial damage, resulting in the release of Cyto-C and the subsequent activation of the caspase cascade, ultimately inducing apoptosis [34].…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Flavonoids and Metformin on Protection of the Methylglyoxal-Induced Damage in PC-12 Neuroblastoma Cells: Structure–Activity Relationship and Potential Target

Zhang,

He,

Wang

et al. 2024

Molecules

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Methylglyoxal-induced ROS elevation is the primary cause of neuronal damage. Metformin is a traditional hypoglycemic drug that has been reported to be beneficial to the nervous system. In this study, flavonoids were found to enhance the protective effect of metformin when added at a molar concentration of 0.5%. The structure–activity relationship (SAR) analysis indicated that ortho- substitution in the B ring, and the absence of double bonds between the 2 and 3 position combined with the gallate substitution with R configuration at the 3 position in the C ring played crucial roles in the synergistic effects, which could be beneficial for designing a combination of the compounds. Additionally, the mechanism study revealed that a typical flavonoid, EGCG, enhanced ROS scavenging and anti-apoptotic ability via the BCL2/Bax/Cyto C/Caspase-3 pathway, and synergistically inhibited the expression of GSK-3β, BACE-1, and APP in PC-12 cells when used in combination with metformin. The dose of metformin used in the combination was only 1/4 of the conventional dose when used alone. These results suggested that ROS-mediated apoptosis and the pathways related to amyloid plaques (Aβ) formation can be the targets for the synergistic neuroprotective effects of flavonoids and metformin.

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Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Flavonoids and Metformin on Protection of the Methylglyoxal-Induced Damage in PC-12 Neuroblastoma Cells: Structure–Activity Relationship and Potential Target

Zhang,

He,

Wang

et al. 2024

Molecules

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A molecular mechanism underlies grass carp (Ctenopharyngodon idella) TARBP2 regulating PKR-mediated cell apoptosis

Li,

Tao,

et al. 2024

Fish & Shellfish Immunology

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Efficient Encapsulation of β-Lapachone into Self-Immolative Polymer Nanoparticles for Cyclic Amplification of Intracellular Reactive Oxygen Species Stress

Guo,

Ding,

et al. 2024

ACS Nano

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The selective upregulation of intracellular oxidative stress in cancer cells presents a promising approach for effective cancer treatment. In this study, we report the integration of enzyme catalytic amplification and chemical amplification reactions in β-lapachone (Lap)-loaded micellar nanoparticles (NPs), which are self-assembled from reactive oxygen species (ROS)-responsive self-immolative polymers (SIPs). This integration enables cyclic amplification of intracellular oxidative stress in cancer cells. Specifically, we have developed ROS-responsive SIPs with phenylboronic ester triggering motifs and hexafluoroisopropanol moieties in the side chains, significantly enhancing Lap loading efficiency (98%) and loading capacity (33%) through multiple noncovalent interactions. Upon ROS activation in tumor cells, the Lap-loaded micellar NPs disassemble, releasing Lap and generating additional ROS via enzyme catalytic amplification. This process elevates intracellular oxidative stress and triggers polymer depolymerization in a positive feedback loop. Furthermore, the degradation of SIPs via chemical amplification produces azaquinone methide intermediates, which consume intracellular thiol-related substrates, disrupt intracellular redox hemostasis, further intensify oxidative stress, and promote cancer cell apoptosis. This work introduces a strategy to enhance intracellular oxidative stress by combining enzymatic and chemical amplification reactions, providing a potential pathway for the development of highly efficient anticancer agents.

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The involvement of ROS-regulated programmed cell death in hepatocellular carcinoma

Cited by 6 publications

References 170 publications

Synergistic Effect of Flavonoids and Metformin on Protection of the Methylglyoxal-Induced Damage in PC-12 Neuroblastoma Cells: Structure–Activity Relationship and Potential Target

Synergistic Effect of Flavonoids and Metformin on Protection of the Methylglyoxal-Induced Damage in PC-12 Neuroblastoma Cells: Structure–Activity Relationship and Potential Target

A molecular mechanism underlies grass carp (Ctenopharyngodon idella) TARBP2 regulating PKR-mediated cell apoptosis

Efficient Encapsulation of β-Lapachone into Self-Immolative Polymer Nanoparticles for Cyclic Amplification of Intracellular Reactive Oxygen Species Stress

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