scholarly journals 8-Methoxypsoralen Induces Intrinsic Apoptosis in HepG2 Cells: Involvement of Reactive Oxygen Species Generation and ERK1/2 Pathway Inhibition

2015 ◽  
Vol 37 (1) ◽  
pp. 361-374 ◽  
Author(s):  
Huan Yang ◽  
Jing Xiong ◽  
Wenjing Luo ◽  
Jian Yang ◽  
Tao Xi
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Hepg2 Cells ◽  
Ros Generation ◽  
Oxygen Species ◽  
Intrinsic Apoptosis ◽  
Induced Apoptosis

Background/Aims: 8-Methoxypsoralen (8-MOP), a formerly considered photosensitizing agent, induces apoptosis when used alone. On this basis, the present study was designed to explore the effects and mechanisms of 8-MOP-induced apoptosis in human hepatocellular carcinoma HepG2 cells, independent of its photoactivation. Methods: We analyzed the cell viability with MTT assay. Flow cytometry was used to examine the apoptosis rate, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation after specific staining. The expression and location of apoptosis-associated protein as well as the activation status of cell signaling pathway were determined by Western blot analysis. Results: 8-MOP significantly decreased cell viability and induced cell apoptosis through mitochondrial apoptotic pathway, as demonstrated by increased Bax/Bcl-2 ratio, collapsed MMP, and induced cytochrome c release (Cyt c) and apoptosis-inducing factor (AIF) transposition. ROS generation was significantly increased by 8-MOP and the eradication of ROS significantly abolished 8-MOP-induced apoptosis. In addition, the activation of ERK1/2 was drastically decreased by 8-MOP as ERK inhibitor PD98059, indicating a role of ERK1/2 signaling pathway in 8-MOP-induced cell apoptosis. Conclusion: 8-MOP induces intrinsic apoptosis by increasing ROS generation and inhibiting ERK1/2 pathway in HepG2 cells. The findings are important in substantiating the anti-tumor role of 8-MOP in cancer therapy.

scholarly journals MiR-4673 Modulates Paclitaxel-Induced Oxidative Stress and Loss of Mitochondrial Membrane Potential by Targeting 8-Oxoguanine-DNA Glycosylase-1

2017 ◽  
Vol 42 (3) ◽  
pp. 889-900 ◽  
Author(s):  
Hai-Li Huang ◽  
Ya-Peng Shi ◽  
Hui-Juan He ◽  
Ya-Hong Wang ◽  
Ting Chen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Membrane Potential ◽  
Cell Viability ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Bioinformatics Analysis ◽  
Dna Glycosylase ◽  
Ros Generation ◽  
Oxygen Species ◽  
Induced Apoptosis

Background: Our previous study identified a novel microRNA, miR-4673, which is upregulated in A549 cells exposed to paclitaxel (PTX). In this study, we investigated the role of miR-4673 in PTX-induced cytotoxicity. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, apoptosis assay, 5,5’,6,6’-Tetrachloro-1,1’,3,3’-tetraethyl-imidacarbocyanine iodide (JC-1) staining and 2’,7’-Dichlorofluorescein (DCFH) staining were used to evaluate cell viability, apoptosis, mitochondrial membrane potential (MMP) loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis and Luciferase reporter assay were used to explore whether 8-oxoguanine-DNA glycosylase-1 (OGG1) is a target gene of miR-4673. Results: Enforced expression of miR-4673 decreased cell viability and increased PTX-induced apoptosis, MMP loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis, which was used to identify potential target of miR-4673, revealed a binding site of miR-4673 in 3’UTR of OGG1. Luciferase reporters assays showed that miR-4673 specifically binds to ‘CUGUUGA’ in 3’UTR of OGG1. Enforced expression of miR-4673 decreased accumulation of OGG1. In addition, silencing OGG1 enhanced inhibitory effects of PTX on apoptosis, MMP loss and ROS generation, which is similar to effects of miR-4673. Moreover, enforced expression of OGG1 compromised promoting effects of miR-4673 on PTX-induced apoptosis, MMP loss and ROS generation. Conclusion: miR-4673 modulates PTX-induced apoptosis, MMP loss and ROS generation by targeting OGG1.

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.

scholarly journals CBIO-07. CELL DEATH INDUCED BY AN OSCILLATING MAGNETIC FIELD IN PATIENT DERIVED GLIOBLASTOMA CELLS IS MEDIATED BY REACTIVE OXYGEN SPECIES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii17-ii17
Author(s):  
Shashank Hambarde ◽  
Martyn Sharpe ◽  
David Baskin ◽  
Santosh Helekar
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cell Viability ◽  
Cortical Neurons ◽  
Reactive Oxygen ◽  
Great Promise ◽  
Antioxidant Vitamin ◽  
Ros Generation ◽  
Oxygen Species ◽  
Novel Therapy

Abstract Noninvasive cancer therapy with minimal side effects would be ideal for improving patient outcome in the clinic. We have developed a novel therapy using strong rotating magnets mounted on a helmet. They generate oscillating magnetic fields (OMF) that penetrate through the skull and cover the entire brain. We have demonstrated that OMF can effectively kill patient derived glioblastoma (GBM) cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes (NHA). Exposure of GBM cells to OMF reduced the cell viability by 33% in comparison to sham-treated cells (p< 0.001), while not affecting NHA cell viability. Time lapse video-microscopy for 16 h after OMF exposure showed a marked elevation of mitochondrial reactive oxygen species (ROS), and rapid apoptosis of GBM cells due to activation of caspase 3. Addition of a potent antioxidant vitamin E analog Trolox effectively blocked OMF-induced GBM cell death. Furthermore, OMF significantly potentiated the cytotoxic effect of the pro-oxidant Benzylamine. The results of our studies demonstrate that OMF-induced cell death is mediated by ROS generation. These results demonstrate a potent oncolytic effect on GBM cells that is novel and unrelated to any previously described therapy, including a very different mechanism of action and different technology compared to Optune therapy. The effect is very powerful, and unlike Optune, can be seen within hours after initiation of treatment. We believe that this technology holds great promise for new, effective and nontoxic treatment of glioblastoma.

scholarly journals A Novel Tetrapeptide Derivative Exhibits In Vitro Inhibition of Neutrophil-Derived Reactive Oxygen Species and Lysosomal Enzymes Release

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Sumitra Miriyala ◽  
Manikandan Panchatcharam ◽  
Meera Ramanujam ◽  
Rengarajulu Puvanakrishnan
Keyword(s):  
Reactive Oxygen Species ◽  
Superoxide Anion ◽  
Lysosomal Enzymes ◽  
Reactive Oxygen ◽  
Peptide Sequence ◽  
Ros Generation ◽  
Oxygen Species ◽  
Complement Factors

Neutrophil infiltration plays a major role in the pathogenesis of myocardial injury. Oxidative injury is suggested to be a central mechanism of the cellular damage after acute myocardial infarction. This study is pertained to the prognostic role of a tetrapeptide derivative PEP1261 (BOC-Lys(BOC)-Arg-Asp-Ser(tBu)-OtBU), a peptide sequence (39–42) of lactoferrin, studied in the modulation of neutrophil functions in vitro by measuring the reactive oxygen species (ROS) generation, lysosomal enzymes release, and enhanced expression of C proteins. The groundwork experimentation was concerned with the isolation of neutrophils from the normal and acute myocardial infarct rats to find out the efficacy of PEP1261 in the presence of a powerful neutrophil stimulant, phorbol 12-myristate 13 acetate (PMA). Stimulation of neutrophils with PMA resulted in an oxidative burst of superoxide anion and enhanced release of lysosomal enzymes and expression of complement proteins. The present study further demonstrated that the free radicals increase the complement factors in the neutrophils confirming the role of ROS. PEP1261 treatment significantly reduced the levels of superoxide anion and inhibited the release of lysosomal enzymes in the stimulated control and infarct rat neutrophils. This study demonstrated that PEP1261 significantly inhibited the effect on the ROS generation as well as the mRNA synthesis and expression of the complement factors in neutrophils isolated from infarct heart.

Extremely enhanced contaminant decomposition catalyzed by hemin via the coupling of persistent free radicals and ascorbic acid

2015 ◽  
Vol 51 (89) ◽  
pp. 16139-16142 ◽  
Author(s):  
Yuyuan Yao ◽  
Bin Jiang ◽  
Yajun Mao ◽  
Juan Chen ◽  
Zhenfu Huang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Ascorbic Acid ◽  
Free Radicals ◽  
Reactive Oxygen ◽  
Environmental Pollutant ◽  
Ros Generation ◽  
Oxygen Species ◽  
Positive Role ◽  
Rate Enhancement

A positive role of PFRs in enhancing reactive oxygen species (ROS) generation for an extreme rate enhancement in environmental pollutant decomposition is reported.

scholarly journals Critical role of caveolin-1 in aflatoxin B1-induced hepatotoxicity via the regulation of oxidation and autophagy

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Qingqiang Xu ◽  
Wenwen Shi ◽  
Pan Lv ◽  
Wenqi Meng ◽  
Guanchao Mao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Aflatoxin B1 ◽  
Cell Apoptosis ◽  
Critical Role ◽  
Hepatic Cell ◽  
Hepatocellular Injury ◽  
Caveolin 1 ◽  
Induced Apoptosis

AbstractAflatoxin B1 (AFB1) is a potent hepatocarcinogen in humans and exposure to AFB1 is known to cause both acute and chronic hepatocellular injury. As the liver is known to be the main target organ of aflatoxin, it is important to identify the key molecules that participate in AFB1-induced hepatotoxicity and to investigate their underlying mechanisms. In this study, the critical role of caveolin-1 in AFB1-induced hepatic cell apoptosis was examined. We found a decrease in cell viability and an increase in oxidation and apoptosis in human hepatocyte L02 cells after AFB1 exposure. In addition, the intracellular expression of caveolin-1 was increased in response to AFB1 treatment. Downregulation of caveolin-1 significantly alleviated AFB1-induced apoptosis and decreased cell viability, whereas overexpression of caveolin-1 reversed these effects. Further functional analysis showed that caveolin-1 participates in AFB1-induced oxidative stress through its interaction with Nrf2, leading to the downregulation of cellular antioxidant enzymes and the promotion of oxidative stress-induced apoptosis. In addition, caveolin-1 was found to regulate AFB1-induced autophagy. This finding was supported by the effect that caveolin-1 deficiency promoted autophagy after AFB1 treatment, leading to the inhibition of apoptosis, whereas overexpression of caveolin-1 inhibited autophagy and accelerated apoptosis. Interestingly, further investigation showed that caveolin-1 participates in AFB1-induced autophagy by regulating the EGFR/PI3K-AKT/mTOR signaling pathway. Taken together, our data reveal that caveolin-1 plays a crucial role in AFB1-induced hepatic cell apoptosis via the regulation of oxidation and autophagy, which provides a potential target for the development of novel treatments to combat AFB1 hepatotoxicity.

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