scholarly journals Small size gold nanoparticles enhance apoptosis-induced by cold atmospheric plasma via depletion of intracellular GSH and modification of oxidative stress

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Paras Jawaid ◽  
Mati Ur Rehman ◽  
Qing-Li Zhao ◽  
Masaki Misawa ◽  
Kenji Ishikawa ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Combined Treatment ◽  
Underlying Mechanism ◽  
Atmospheric Plasma ◽  
Ros Generation ◽  
Au Nps ◽  
Cold Atmospheric Plasma ◽  
Synergistic Enhancement ◽  
Intracellular Ros ◽  
Induced Apoptosis

Abstract Gold nanoparticles (Au-NPs) have attracted attention as a promising sensitizer owing to their high atomic number (Z), and because they are considered fully multifunctional, they are preferred over other metal nanoparticles. Cold atmospheric plasma (CAP) has also recently gained attention, especially for cancer treatment, by inducing apoptosis through the formation of reactive oxygen species (ROS). In this study, the activity of different sized Au-NPs with helium-based CAP (He-CAP) was analyzed, and the underlying mechanism was investigated. Treating cells with only small Au-NPs (2 nm) significantly enhanced He-CAP-induced apoptosis. In comparison, 40 nm and 100 nm Au-NPs failed to enhance cell death. Mechanistically, the synergistic enhancement was due to 2 nm Au-NPs-induced decrease in intracellular glutathione, which led to the generation of intracellular ROS. He-CAP markedly induced ROS generation in an aqueous medium; however, treatment with He-CAP alone did not induce intracellular ROS formation. In contrast, the combined treatment significantly enhanced the intracellular formation of superoxide (O2• −) and hydroxyl radical (•OH). These findings indicate the potential therapeutic use of Au-NPs in combination with CAP and further clarify the role of Au-NPs in He-CAP-aided therapies.

scholarly journals Evaluation of anticancer activity in vitro of a stable copper(I) complex with phosphine-peptide conjugate

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Urszula K. Komarnicka ◽  
Barbara Pucelik ◽  
Daria Wojtala ◽  
Monika K. Lesiów ◽  
Grażyna Stochel ◽  
...  
Keyword(s):  
A549 Cells ◽  
Ros Generation ◽  
Dependent Manner ◽  
Hacat Cells ◽  
Icp Ms ◽  
Intracellular Ros ◽  
M Phase ◽  
Lung Adenocarcinoma A549 ◽  
Induced Apoptosis

Abstract[CuI(2,9-dimethyl-1,10-phenanthroline)P(p-OCH3-Ph)2CH2SarcosineGlycine] (1-MPSG), highly stable in physiological media phosphino copper(I) complex—is proposed herein as a viable alternative to anticancer platinum-based drugs. It is noteworthy that, 1-MPSG significantly and selectively reduced cell viability in a 3D spheroidal model of human lung adenocarcinoma (A549), in comparison with non-cancerous HaCaT cells. Confocal microscopy and an ICP-MS analysis showed that 1-MPSG effectively accumulates inside A549 cells with colocalization in mitochondria and nuclei. A precise cytometric analysis revealed a predominance of apoptosis over the other types of cell death. In the case of HaCaT cells, the overall cytotoxicity was significantly lower, indicating the selective activity of 1-MPSG towards cancer cells. Apoptosis also manifested itself in a decrease in mitochondrial membrane potential along with the activation of caspases-3/9. Moreover, the caspase inhibitor (Z-VAD-FMK) pretreatment led to decreased level of apoptosis (more pronouncedly in A549 cells than in non-cancerous HaCaT cells) and further validated the caspases dependence in 1-MPSG-induced apoptosis. Furthermore, the 1-MPSG complex presumably induces the changes in the cell cycle leading to G2/M phase arrest in a dose-dependent manner. It was also observed that the 1-MPSG mediated intracellular ROS alterations in A549 and HaCaT cells. These results, proved by fluorescence spectroscopy, and flow cytometry, suggest that investigated Cu(I) compound may trigger apoptosis also through ROS generation.

Deferasirox Inhibit Doxorubicin-Induced Reactive Oxygen Species Generation in Both Acute Myeloid Leukemia and Normal Heart Cell While Maintain the Cytotoxicity of Doxorubicin Only on Acute Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3620-3620
Author(s):  
Su-Peng Yeh ◽  
Yu-Chien Chang ◽  
Wen-Jyi Lo ◽  
Min-Lih Huang ◽  
Yang-Sheng Yang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Line ◽  
Myeloid Leukemia ◽  
Heart Cell ◽  
Ros Generation ◽  
Heart Cells ◽  
Normal Heart ◽  
Intracellular Ros ◽  
Induced Apoptosis ◽  
Acute Myeloid

Abstract Abstract 3620 Background: Deferasirox (DFX) was recently found to have anti-leukemia effect both in vitro and in vivo. DFX can also potently inhibit the generation of intracellular reactive oxygen species (ROS). On the other hand, the generation of ROS by Doxorubicin (DOX) is critical for the cytotoxicity on both leukemia and normal heart cells. It is not known whether combining DFX and DOX will have synergistic or antagonizing effect on leukemic cells. Similarly, it is also unknown whether adding DFX to DOX will have protective effect on normal heart cell. Method: Cells of human acute myeloid leukemia (AML) cell line THP1, mice AML cell line WEHI3, and rat normal heart cell line H9C2 were treated with Doxorubicin 5microM for various duration in the presence of absence of DFX pretreatment (100microM for 10 minutes). Intracellular ROS generation was measured by the detection of 2,7-dichlorodihydrofluorescein (DCF) fluorescence intensity using flow cytometry. Apoptosis was determined by Annexin V-Propidium Iodide staining using flow cytometry. Cytotoxicity was determined by Trypan blue exclusion assay. Results: Although intracellular ROS was reduced, DFX alone induced apoptosis of THP1 (from 3% to 18%) and WEHI3 (from 31% to 49%) AML cells. DOX-induced ROS production was also significantly reduced when THP1, WEHI3, and H9C2 cells were pretreated with DFX (Figure 1a, 1b, 1c respectively). However, the DOX-induced apoptosis of THP1 and WEHI3 AML cells were not antagonized by DFX (Figure 2a). 24 hours after exposure to this physiological dose DOX, all the WEHI3 cells died in both DFX treated or untreated group (figure 2b). More importantly, DFX-pretreated H9C2 heart cells had fewer cell death (3.7%) after exposure to DOX (5microM for 24 hours) compared to non-DFX pretreated cells (8.5%). Conclusions: DFX alone induced apoptosis in two different AML cell lines. DFX also markedly reduced the ROS generation due to DOX treatment. However, DFX did not negatively influence the pro-apoptotic and cytotoxic effect of DOX on these AML cell lines. Interestingly, DFX also markedly reduced the DOX-induced ROS generation and DOX-induced cell death in normal rat heart cell, which might have protective effect on DOX-related cardiomyopathy. We are now using Balb/c-WEHI3 AML mice model to test whether DFX can protect cardiomyocytes from DOX-related damage while maintain the cytotoxic effect of DOX on AML cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Novel Antioxidant Compound JSH-23 Prevents Osteolysis by Scavenging ROS During Both Osteoclastogenesis and Osteoblastogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Liangwei Mei ◽  
Yi Zheng ◽  
Teng Ma ◽  
Bing Xia ◽  
Xue Gao ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Ros Generation ◽  
Protective Effects ◽  
Bone Homeostasis ◽  
Skeletal Disease ◽  
Antioxidant Compound ◽  
Intracellular Ros ◽  
Enhanced Expression ◽  
Induced Apoptosis

Inflammatory osteolysis is a pathological skeletal disease associated with not only the production of inflammatory cytokines but also local oxidative status. Excessive reactive oxygen species (ROS) promote bone resorption by osteoclasts and induce the apoptosis of osteoblasts. In consideration of the lack of effective preventive or treatments options against osteolysis, the exploitation of novel pharmacological compounds/agents is critically required. In our study, we found that a novel antioxidant compound, JSH-23, plays a role in restoring bone homeostasis by scavenging intracellular ROS during both osteoclastogenesis and osteoblastogenesis. Mechanically, JSH-23 suppressed RANKL-induced osteoclastogenesis, bone resorption and the expression of specific genes (including NFATc1, c-Fos, TRAP, CTSK and DC-STAMP) via inhibition of the NF-κB signaling pathway. Meanwhile, JSH-23 suppressed RANKL-induced ROS generation via the TRAF6/Rac1/NOX1 pathway and the enhanced expression of Nrf2/HO-1. In addition, JSH-23 attenuated H2O2-induced apoptosis and mineralization reduction in osteoblasts by reducing ROS production and enhancing Nrf2/HO-1 expression. Our in vivo results further revealed that JSH-23 exerts its protective effects on bone mass through its antioxidant activity. In conclusion, our results show that the application of JSH-23 might be a novel and plausible strategy for the treatment of osteolysis-related disease.

Bactericidal efficacy of cold atmospheric plasma treatment against multidrug-resistant Pseudomonas aeruginosa

2020 ◽  
Vol 15 (2) ◽  
pp. 115-125 ◽  
Author(s):  
Liyun Wang ◽  
Chuankai Xia ◽  
Yajun Guo ◽  
Chunjun Yang ◽  
Cheng Cheng ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Multidrug Resistant ◽  
Atmospheric Plasma ◽  
Resistant Bacteria ◽  
Cold Atmospheric Plasma ◽  
Bactericidal Efficacy ◽  
Drug Resistant Bacteria ◽  
Intracellular Ros ◽  
Ros Scavengers

Aim: The global of spread multidrug-resistant Pseudomonas aeruginosa has become a public health threat. Cold atmospheric plasma (CAP) is reported to have bactericidal efficacy; however, its effects on clinical super multidrug-resistant P. aeruginosa are unclear. The aim of this study was to investigate the bactericidal efficacy of CAP on a strain of super multidrug-resistant P. aeruginosa. Materials & methods: The effects of CAP treatments were evaluated using assays for the detection of growth, viability, metabolism, virulence factors and reactive oxygen species (ROS) levels. Results: Both CAP treatments dose-dependently inhibited cell viability and metabolic activity, and decreased the expression of several virulence factors. CAP treatment induced a significant increase in intracellular ROS levels, and ROS scavengers inhibited this effect. Conclusion: CAP treatment is a promising option for the clinical inhibition of multidrug-resistant P. aeruginosa, and the development of CAP technologies might be the key to solving the long-standing problem of drug-resistant bacteria.

scholarly journals Inhibition of Autophagy Promotes Hemistepsin A-Induced Apoptosis via Reactive Oxygen Species-Mediated AMPK-Dependent Signaling in Human Prostate Cancer Cells

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1806
Author(s):  
Kwang-Youn Kim ◽  
Un-Jung Yun ◽  
Seung-Hee Yeom ◽  
Sang-Chan Kim ◽  
Hu-Jang Lee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Xenograft Model ◽  
Underlying Mechanism ◽  
Ros Generation ◽  
Prostate Cancer Cells ◽  
Ros Scavenger ◽  
Induced Apoptosis

Chemotherapy is an essential strategy for cancer treatment. On the other hand, consistent exposure to chemotherapeutic drugs induces chemo-resistance in cancer cells through a variety of mechanisms. Therefore, it is important to develop a new drug inhibiting chemo-resistance. Although hemistepsin A (HsA) is known to have anti-tumor effects, the molecular mechanisms of HsA-mediated cell death are unclear. Accordingly, this study examined whether HsA could induce apoptosis in aggressive prostate cancer cells, along with its underlying mechanism. Using HsA on two prostate cancer cell lines, PC-3 and LNCaP cells, the cell analysis and in vivo xenograft model were assayed. In this study, HsA induced apoptosis and autophagy in PC-3 cells. HsA-mediated ROS production attenuated HsA-induced apoptosis and autophagy after treatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. Moreover, autophagy inhibition by 3-MA or CQ is involved in accelerating the apoptosis induced by HsA. Furthermore, we showed the anti-tumor effects of HsA in mice, as assessed by the reduced growth of the xenografted tumors. In conclusion, HsA induced apoptosis and ROS generation, which were blocked by protective autophagy signaling.

Reactive oxygen species-initiated autophagy opposes aldosterone-induced podocyte injury

2016 ◽  
Vol 310 (7) ◽  
pp. F669-F678 ◽  
Author(s):  
Mi Bai ◽  
Ruochen Che ◽  
Yue Zhang ◽  
Yanggang Yuan ◽  
Chunhua Zhu ◽  
...  
Keyword(s):  
Kidney Diseases ◽  
Annexin V ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Ros Generation ◽  
Dependent Manner ◽  
Related Gene ◽  
Podocyte Injury ◽  
Induced Apoptosis

Evidence has demonstrated that aldosterone (Aldo) is involved in the development and progression of chronic kidney diseases. The purpose of the present study was to investigate the role of autophagy in Aldo-induced podocyte damage and the underlying mechanism. Mouse podocytes were treated with Aldo in the presence or absence of 3-methyladenine and N-acetylcysteine. Cell apoptosis was investigated by detecting annexin V conjugates, apoptotic bodies, caspase-3 activity, and alterations of the podocyte protein nephrin. Autophagy was evaluated by measuring the expressions of light chain 3, p62, beclin-1, and autophagy-related gene 5. Aldo (10−7 mol/l) induced podocyte apoptosis, autophagy, and downregulation of nephrin protein in a time-dependent manner. Aldo-induced apoptosis was further promoted by the inhibition of autophagy via 3-methyladenine and autophagy-related gene 5 small interfering RNA pretreatment. Moreover, Aldo time dependently increased ROS generation, and H2O2 (10−4 mol/l) application remarkably elevated podocyte autophagy. After treatment with N-acetylcysteine, the autophagy induced by Aldo or H2O2 was markedly attenuated, suggesting a key role of ROS in mediating autophagy formation in podocytes. Inhibition of ROS could also lessen Aldo-induced podocyte injury. Taken together, our findings suggest that ROS-triggered autophagy played a protective role against Aldo-induced podocyte injury, and targeting autophagy in podocytes may represent a new therapeutic strategy for the treatment of podocytopathy.

scholarly journals Low dose Cold Atmospheric Plasma induces membrane oxidation, stimulates endocytosis and enhances uptake of nanomaterials in Glioblastoma multiforme cells

2019 ◽  
Author(s):  
Zhonglei He ◽  
Kangze Liu ◽  
Laurence Scally ◽  
Eline Manaloto ◽  
Sebnem Gunes ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Membrane Damage ◽  
Cellular Membrane ◽  
Atmospheric Plasma ◽  
Ros Generation ◽  
Main Role ◽  
Cancer Therapies ◽  
Membrane Repair ◽  
Cold Atmospheric Plasma ◽  
Therapy And Diagnosis

AbstractCold atmospheric plasma (CAP) has demonstrated synergistic cytotoxic effects with nanoparticles, especially promoting the uptake and accumulation of nanoparticles inside cells. However, the mechanisms driving the effects need to be explored. In this study, we investigate the enhanced uptake of theranostic nanomaterials by CAP. Numerical modelling of the uptake of gold nanoparticle into U373MG Glioblastoma multiforme (GBM) cells predicts that CAP may introduce a new uptake route. We demonstrate that cell membrane repair pathways play the main role in this stimulated new uptake route, following non-toxic doses of dielectric barrier discharge CAP (30 s, 75 kV). CAP treatment induces cellular membrane damage, mainly via lipid peroxidation as a result of reactive oxygen species (ROS) generation. Membranes rich in peroxidated lipids are then trafficked into cells via membrane repairing endocytosis. We confirm that the enhanced uptake of nanomaterials is clathrin-dependent using chemical inhibitors and silencing of gene expression. Therefore, CAP-stimulated membrane repair increases endocytosis and accelerates the uptake of gold nanoparticles into U373MG cells after CAP treatment. Our data demonstrate the utility of CAP to model membrane oxidative damage in cells and characterise a previously unreported mechanism of membrane repair to trigger nanomaterial uptake which will be useful for developing more efficient deliveries of nanoparticles and pharmaceuticals into cancer cells for tumour therapy and diagnosis. This mechanism of RONS-induced endocytosis will also be of relevance to other cancer therapies that induce an increase in extracellular RONS.

scholarly journals Baicalin Augments Hyperthermia-Induced Apoptosis in U937 Cells and Modulates the MAPK Pathway via ROS Generation

2018 ◽  
Vol 45 (6) ◽  
pp. 2444-2460 ◽  
Author(s):  
Shahbaz Ahmad Zakki ◽  
Zheng-Guo Cui ◽  
Lu Sun ◽  
Qian-Wen Feng ◽  
Meng-Ling Li ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Flow Cytometry ◽  
Cell Viability ◽  
Mapk Pathway ◽  
Combined Treatment ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
U937 Cells ◽  
Oxygen Species ◽  
Induced Apoptosis

Background/Aims: Hyperthermia is a widely used therapeutic tool for cancer therapy and a well-known inducer of apoptosis. Although the flavonoid compound baicalin (BCN) is a potent anticancer agent for several human carcinomas, it is less potent in the human U937 myelomonocytic leukemia cell line. To explore any enhancing effects of BCN on hyperthermia-induced apoptosis, this study investigated the combined effects and apoptotic mechanisms of hyperthermia and BCN in U937 cells. Methods: U937 cells were heat treated at 44ºC for 12 min with or without pre-treatment with BCN (10-50 µM) and then incubated for 6 h at 37 ºC with 5% CO2 and 95% air. Cell viability was analyzed by Trypan blue exclusion assay. Apoptosis was examined by DNA fragmentation, fluorescence microscopy and flow cytometry. Generation of mitochondrial trans-membrane potential (MMP), mitochondrial calcium, and reactive oxygen species (ROS) was also detected by flow cytometry. The expression of proteins related to apoptosis and signaling pathways was determined by western blotting. Results: Hyperthermia alone did not reduce cell viability or induce notable levels of apoptosis, but combined hyperthermia and BCN treatment markedly augmented apoptosis by upregulating proapoptotic proteins and suppressing antiapoptotic proteins, culminating in caspase-3 activation. Mitochondrial transmembrane potential was significantly decreased, and generation of reactive oxygen species (ROS) and suppression of antioxidant enzymes were marked. Furthermore, with the combined treatment, the phosphorylated forms of JNK and p38 showed increased expression, whereas AKT was dephosphorylated. JNK-IN-8 (a JNK inhibitor) and NAC (a ROS scavenger) abrogated the apoptotic effects of the combined treatment, significantly protecting the cells and indicating the involvement of high ROS generation and the MAPK pathway in the underlying molecular mechanism. Conclusion: This study provides compelling evidence that hyperthermia, in combination with BCN, is a promising therapeutic strategy for enhancement of apoptosis and suggest a promising therapeutic approach for cancer.

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