scholarly journals Synergistic Antifungal Activity of Isoquercitrin: Apoptosis and Membrane Permeabilization Related to Reactive Oxygen Species inCandida albicans

IUBMB Life ◽  
2018 ◽  
Vol 71 (2) ◽  
pp. 283-292 ◽  
Author(s):  
Suhyun Kim ◽  
Eun-Rhan Woo ◽  
Dong Gun Lee
Keyword(s):  
Reactive Oxygen Species ◽  
Antifungal Activity ◽  
Reactive Oxygen ◽  
Membrane Permeabilization ◽  
Oxygen Species ◽  
Incandida Albicans

scholarly journals Reactive oxygen species (ROS) mediated enhanced anti-candidal activity of ZnS–ZnO nanocomposites with low inhibitory concentrations

RSC Advances ◽  
2015 ◽  
Vol 5 (94) ◽  
pp. 76718-76728 ◽  
Author(s):  
P. Suyana ◽  
S. Nishanth Kumar ◽  
Nimisha Madhavan ◽  
B. S. Dileep Kumar ◽  
Balagopal N. Nair ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Reactive Oxygen Species ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Candida Tropicalis ◽  
Yeast Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Precipitation Technique

Enhanced antifungal activity against the yeast species Candida albicans, Candida tropicalis and Saccharomyces cerevisiae was displayed by ZnS–ZnO nanocomposites prepared by a simple precipitation technique.

scholarly journals Lysosome Membrane Permeabilization Causes Cell Death in Primary Chronic Lymphocytic Leukemia Cells

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 930-930 ◽  
Author(s):  
Rebecca Dielschneider ◽  
Hannah Eisenstat ◽  
James B. Johnston ◽  
Spencer B Gibson
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Chronic Lymphocytic Leukemia ◽  
Peripheral Blood ◽  
Reactive Oxygen ◽  
Membrane Permeabilization ◽  
Lymphocytic Leukemia ◽  
Oxygen Species ◽  
Lysosome Membrane

Abstract Introduction: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in North America. Despite many therapeutic advances over the past decade, drug resistance and disease recurrence are common. Novel therapeutic approaches are therefore required to treat CLL. One novel target identified in a variety of cancers, including acute myeloid leukemia, is the lysosome. In transformed cancerous cells, lysosomes were found to be sensitive to permeabilization by lysotropic agents in a process called lysosome membrane permeabilization. Permeabilization of lysosomes releases their acidic and proteolytic contents into the cytoplasm causing lysosome-mediated cell death. The therapeutic strategy of targeting lysosomes has yet to be determined in CLL. Methods: Primary CLL cells were purified from patient peripheral blood using negative selection and separated on a ficoll gradient. Three different lysosome-targeting drugs used in the clinic for other purposes were investigated: a quinolone, a fluoroquinolone antibiotic, and a cationic drug (CAD). To determine the mechanism of action, various dyes were used to stain lysosomes, mitochondria, and reactive oxygen species. Fluorescence was visualized under the confocal microscope and quantified using flow cytometry. To determine the role of reactive oxygen species (ROS) the antioxidants α-tocopherol, lycopene, N-acetyl cysteine, and glutathione were added to cells. To determine the role of proteases the inhibitors zVADfmk, Ca-074-Me, Chymostatin, and E64 were added to cells. Results: All the lysotropic agents except the antibiotic effectively killed CLL cells isolated from patients. The CAD had the greatest activity and was significantly more cytotoxic to the CLL cells as compared to T cells from the same patients and peripheral blood mononuclear cells from non-CLL donors. Treatment was equally effective in p53-proficient and p53-deficient CLL cells, demonstrating that the most aggressive and drug-resistant CLL cells were sensitive to this CAD. Mechanistic studies revealed that lysosome membrane permeabilization occurred within minutes and led to an increase in ROS and loss of mitochondrial membrane potential. The permeabilization of lysosomes was further confirmed by the translocation of transcription factor EB (TFEB) into the nucleus indicating promotion of lysosomal biogenesis. Lipid ROS were necessary to induce cell death, as only lipophilic antioxidants prevented cell death. Lipophilic antioxidants did not prevent lysosomal permeabilization, but did prevent downstream mitochondrial dysfunction. Inhibitors of caspases and lysosomal cathepsins failed to prevent cell death in CLL cells. Conclusions: Results show that the lysosome-targeting quinolone and CAD effectively permeabilize lysosomes and induce lysosome-mediated cell death in primary human CLL cells. This unique mechanism of cell death in CLL is dependent on the generation of lipid ROS, but not on the action of caspases or cathepsins. Overall, targeting lysosomes may be an effective strategy to selectively kill CLL cells regardless of p53 expression. Future studies are focused on the lysosomal differences in B cells and CLL cells. Disclosures No relevant conflicts of interest to declare.

scholarly journals Proteomics Reveals Octyl Gallate as an Environmentally Friendly Wood Preservative Leading to Reactive Oxygen Species-Driven Metabolic Inflexibility and Growth Inhibition in White-Rot Fungi (Lenzites betulina and Trametes versicolor)

2021 ◽  
Vol 7 (2) ◽  
pp. 145
Author(s):  
Jin-Wei Xu ◽  
Chen-Chung Liao ◽  
Ke-Chang Hung ◽  
Zhong-Yao Wang ◽  
Yu-Tang Tung ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Antifungal Activity ◽  
Trametes Versicolor ◽  
Reactive Oxygen ◽  
White Rot Fungi ◽  
Environmentally Friendly ◽  
White Rot ◽  
Oxygen Species ◽  
Wood Preservatives ◽  
Lenzites Betulina

The most commonly applied wood preservatives are based on creosote, pentachlorophenol, and waterborne chromate copper arsenate, which negatively affect the environment. Thus, environmentally friendly wood preservatives are required. This study investigated the antifungal activity and mechanism of several long-chain alkyl gallates (3,4,5-trihydroxybenzoates) against white-rot fungi, Lenzites betulina and Trametes versicolor. The results revealed that octyl gallate (OG) had the best antifungal activity. Additionally, OG may have a mechanism of action similar to surfactants and inhibit ATPase activity, causing mitochondrial dysfunction and endogenous reactive oxygen species (ROS) production. Upon exposure to endogenous ROS, cells rapidly inhibit the synthesis of 60S ribosomal subunits, thus reducing the mycelial growth rate. L. betulina and T. versicolor also remodeled their energy metabolism in response to low ATP levels and endogenous ROS. After OG treatment, ATP citrate synthase activity was downregulated and glycolytic activity was upregulated in L. betulina. However, the activity of aerobic pathways was decreased and the oxidative branch of the pentose phosphate pathway was redirected form nicotinamide adenine dinucleotide phosphate (NADPH) to minimize endogenous ROS-mediated damage in T. versicolor. Taken together, these observations reveal that OG is a potent inhibitor of white-rot fungus. Further structural optimization research and pharmacological investigations are warranted.

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