scholarly journals Anticancer Activity of Lesbicoumestan in Jurkat Cells via Inhibition of Oxidative Stress-Mediated Apoptosis and MALT1 Protease

Molecules ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 185
Author(s):  
Joo-Eun Lee ◽  
Fang Bo ◽  
Nguyen Thi Thanh Thuy ◽  
Jaewoo Hong ◽  
Ji Shin Lee ◽  
...  
Keyword(s):  
Jurkat Cell ◽  
Three Dimensional ◽  
Jurkat Cells ◽  
Human Leukemia ◽  
Oxygen Species ◽  
Cell Resistance ◽  
Mitochondrial Reactive Oxygen Species ◽  
Mitochondrial Depolarization ◽  
Antiproliferative Effects ◽  
Anticancer Effects

This study explores the potential anticancer effects of lesbicoumestan from Lespedeza bicolor against human leukemia cancer cells. Flow cytometry and fluorescence microscopy were used to investigate antiproliferative effects. The degradation of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) was evaluated using immunoprecipitation, Western blotting, and confocal microscopy. Apoptosis was investigated using three-dimensional (3D) Jurkat cell resistance models. Lesbicoumestan induced potent mitochondrial depolarization on the Jurkat cells via upregulated expression levels of mitochondrial reactive oxygen species. Furthermore, the underlying apoptotic mechanisms of lesbicoumestan through the MALT1/NF-κB pathway were comprehensively elucidated. The analysis showed that lesbicoumestan significantly induced MALT1 degradation, which led to the inhibition of the NF-κB pathway. In addition, molecular docking results illustrate how lesbicoumestan could effectively bind with MALT1 protease at the latter’s active pocket. Similar to traditional 2D cultures, apoptosis was markedly induced upon lesbicoumestan treatment in 3D Jurkat cell resistance models. Our data support the hypothesis that lesbicoumestan is a novel inhibitor of MALT1, as it exhibited potent antiapoptotic effects in Jurkat cells.

Oxidative stress-mediated antiproliferative effects of furan-containing sulfur flavors in human leukemia Jurkat cells

2015 ◽  
Vol 180 ◽  
pp. 1-8 ◽  
Author(s):  
Gong-Liang Zhang ◽  
Ying Liang ◽  
Jun-Ya Zhu ◽  
Qiong Jia ◽  
Wei-Qi Gan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Jurkat Cells ◽  
Human Leukemia ◽  
Antiproliferative Effects

scholarly journals Fisetin Inhibits NLRP3 Inflammasome by Suppressing TLR4/MD2-Mediated Mitochondrial ROS Production

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1215
Author(s):  
Ilandarage Menu Neelaka Molagoda ◽  
Athapaththu Mudiyanselage Gihan Kavinda Athapaththu ◽  
Yung Hyun Choi ◽  
Cheol Park ◽  
Cheng-Yung Jin ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Mammalian Species ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Zebrafish Model ◽  
Anticancer Effects ◽  
Mitochondrial Ros ◽  
Therapeutic Properties ◽  
The Brain

Fisetin has numerous therapeutic properties, such as anti-inflammatory, antioxidative, and anticancer effects. However, the mechanism by which fisetin inhibits NLRP3 inflammasome remains unclear. In this study, we observed that fisetin bound to TLR4 and occluded the hydrophobic pocket of MD2, which in turn inhibited the binding of LPS to the TLR4/MD2 complex. This prevented the initiation of scaffold formation by the inhibition of MyD88/IRAK4 and subsequently downregulated the NF-κB signaling pathway. The result also demonstrated that fisetin downregulated the activation of the NLRP3 inflammasome induced by LPS and ATP (LPS/ATP) and the subsequent maturation of IL-1β. Fisetin also activated mitophagy and prevented the accumulation of damaged mitochondria and the excessive production of mitochondrial reactive oxygen species. The transient knockdown of p62 reversed the inhibitory activity of fisetin on the LPS/ATP-induced formation of the NLRP3 inflammasome. This indicated that fisetin induces p62-mediated mitophagy for eliminating damaged mitochondria. Recently, the existence of inflammasomes in non-mammalian species including zebrafish have been identified. Treatment of an LPS/ATP-stimulated zebrafish model with fisetin aided the recovery of the impaired heart rate, decreased the recruitment of macrophage to the brain, and gradually downregulated the expression of inflammasome-related genes. These results indicated that fisetin inhibited the TLR4/MD2-mediated activation of NLRP3 inflammasome by eliminating damaged mitochondria in a p62-dependent manner.

Silver nanoparticles induce apoptosis via NOX4-derived mitochondrial reactive oxygen species and endoplasmic reticulum stress in colorectal cancer cells

Nanomedicine ◽  
2021 ◽  
Author(s):  
Juan-Hua Quan ◽  
Fei Fei Gao ◽  
Jia-Qi Chu ◽  
Guang-Ho Cha ◽  
Jae-Min Yuk ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Reactive Oxygen Species ◽  
Er Stress ◽  
Stress Responses ◽  
Hct116 Cell ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Anticancer Effects ◽  
Species Production

Aim: To investigate the anticancer mechanisms of silver nanoparticles (AgNPs) in colorectal cancer. Methods: Anticancer effects of AgNPs were determined in colorectal cancer HCT116 cells and xenograft mice using cellular and molecular methods. Results: AgNPs induced mitochondrial reactive oxygen species production, mitochondrial dysfunction and endoplasmic reticulum (ER) stress responses through NOX4 and led to HCT116 cell apoptosis. Pretreatment with DPI or 4-PBA significantly inhibited mitochondrial reactive oxygen species production, apoptosis, ER stress response, NOX4 expression and mitochondrial dysfunction in AgNP-treated HCT116 cells. AgNPs also significantly suppressed HCT116 cell-based xenograft tumor growth in nude mice by inducing apoptosis and ER stress responses. Conclusion: AgNPs exert anticancer effects against colorectal cancer via ROS- and ER stress-related mitochondrial apoptosis pathways.

scholarly journals Dihydroceramide accumulation and reactive oxygen species are distinct and nonessential events in 4-HPR-mediated leukemia cell death

2012 ◽  
Vol 90 (2) ◽  
pp. 209-223 ◽  
Author(s):  
Aintzane Apraiz ◽  
Jolanta Idkowiak-Baldys ◽  
Naiara Nieto-Rementería ◽  
María Dolores Boyano ◽  
Yusuf A Hannun ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Vitamin E ◽  
Leukemia Cell ◽  
Reactive Oxygen ◽  
Jurkat Cells ◽  
Human Leukemia ◽  
Ros Production ◽  
Oxygen Species ◽  
Independent Events

4-(Hydroxyphenyl)retinamide (4-HPR) is a synthetic retinoid with a strong apoptotic effect towards different cancer cell lines in vitro, and it is currently tested in clinical trials. Increases of reactive oxygen species (ROS) and modulation of endogenous sphingolipid levels are well-described events observed upon 4-HPR treatment, but there is still a lack of understanding of their relationship and their contribution to cell death. LC–MS analysis of sphingolipids revealed that in human leukemia CCRF-CEM and Jurkat cells, 4-HPR induced dihydroceramide but not ceramide accumulation even at sublethal concentrations. Myriocin prevented the 4-HPR-induced dihydroceramide accumulation, but it did not prevent the loss of viability and increase of intracellular ROS production. On the other hand, ascorbic acid, Trolox, and vitamin E reversed 4-HPR effects on cell death but not dihydroceramide accumulation. NDGA, described as a lipoxygenase inhibitor, exerted a significantly higher antioxidant activity than vitamin E and abrogated 4-HPR-mediated ROS. It did not however rescue cellular viability. Taken together, this study demonstrates that early changes observed upon 4-HPR treatment, i.e., sphingolipid modulation and ROS production, are mechanistically independent events. Furthermore, the results indicate that 4-HPR-driven cell death may occur even in the absence of dihydroceramide or ROS accumulation. These observations should be taken into account for an improved design of drug combinations.

scholarly journals Unique Cellular and Biochemical Features of Human Mitochondrial Peroxiredoxin 3 Establish the Molecular Basis for Its Specific Reaction with Thiostrepton

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 150
Author(s):  
Kimberly J. Nelson ◽  
Terri Messier ◽  
Stephanie Milczarek ◽  
Alexis Saaman ◽  
Stacie Beuschel ◽  
...  
Keyword(s):  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Wild Type ◽  
Cellular Models ◽  
Chemotherapeutic Approach ◽  
Promising Target ◽  
Redox Responsive ◽  
Catalytic Cysteine ◽  
Increased Sensitivity ◽  
Peroxiredoxin 3

A central hallmark of tumorigenesis is metabolic alterations that increase mitochondrial reactive oxygen species (mROS). In response, cancer cells upregulate their antioxidant capacity and redox-responsive signaling pathways. A promising chemotherapeutic approach is to increase ROS to levels incompatible with tumor cell survival. Mitochondrial peroxiredoxin 3 (PRX3) plays a significant role in detoxifying hydrogen peroxide (H2O2). PRX3 is a molecular target of thiostrepton (TS), a natural product and FDA-approved antibiotic. TS inactivates PRX3 by covalently adducting its two catalytic cysteine residues and crosslinking the homodimer. Using cellular models of malignant mesothelioma, we show here that PRX3 expression and mROS levels in cells correlate with sensitivity to TS and that TS reacts selectively with PRX3 relative to other PRX isoforms. Using recombinant PRXs 1–5, we demonstrate that TS preferentially reacts with a reduced thiolate in the PRX3 dimer at mitochondrial pH. We also show that partially oxidized PRX3 fully dissociates to dimers, while partially oxidized PRX1 and PRX2 remain largely decameric. The ability of TS to react with engineered dimers of PRX1 and PRX2 at mitochondrial pH, but inefficiently with wild-type decameric protein at cytoplasmic pH, supports a novel mechanism of action and explains the specificity of TS for PRX3. Thus, the unique structure and propensity of PRX3 to form dimers contribute to its increased sensitivity to TS-mediated inactivation, making PRX3 a promising target for prooxidant cancer therapy.

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