scholarly journals Endogenous Reactive Oxygen Species Is an Important Mediator of Miconazole Antifungal Effect

2002 ◽  
Vol 46 (10) ◽  
pp. 3113-3117 ◽  
Author(s):  
Daisuke Kobayashi ◽  
Kei Kondo ◽  
Nobuyuki Uehara ◽  
Seiko Otokozawa ◽  
Naoki Tsuji ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Ros Production ◽  
Oxygen Species ◽  
Antifungal Effect ◽  
Fourfold Increase ◽  
Endogenous Reactive Oxygen Species ◽  
Important Mediator ◽  
Dose Dependent

ABSTRACT We investigated the significance of endogenous reactive oxygen species (ROS) produced by fungi treated with miconazole. ROS production in Candida albicans was measured by a real-time fluorogenic assay. The level of ROS production was increased by miconazole at the MIC (0.125 μg/ml) and was enhanced further in a dose-dependent manner, with a fourfold increase detected when miconazole was used at 12.5 μg/ml. This increase in the level of ROS production was completely inhibited by pyrrolidinedithiocarbamate (PDTC), an antioxidant, at 10 μM. In a colony formation assay, the decrease in cell viability associated with miconazole treatment was significantly prevented by addition of PDTC. Moreover, the level of ROS production by 10 clinical isolates of Candida species was inversely correlated with the miconazole MIC (r = −0.8818; P < 0.01). These results indicate that ROS production is important to the antifungal activity of miconazole.

scholarly journals Erigeron annuus (L.) Pers. Extract Inhibits Reactive Oxygen Species (ROS) Production and Fat Accumulation in 3T3-L1 Cells by Activating an AMP-Dependent Kinase Signaling Pathway

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 139 ◽  
Author(s):  
Yoon-Hee Choi ◽  
Ok-Hwan Lee ◽  
Yulong Zheng ◽  
Il-Jun Kang
Keyword(s):  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Water Extract ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Ros Production ◽  
Oxygen Species ◽  
Fat Accumulation ◽  
Ampk Signaling ◽  
Erigeron Annuus

Obesity is one of the major public health problems in the world because it is implicated in metabolic syndromes, such as type 2 diabetes, hypertension, and cardiovascular diseases. The objective of this study was to investigate whether Erigeron annuus (L.) Pers. (EAP) extract suppresses reactive oxygen species (ROS) production and fat accumulation in 3T3-L1 cells by activating an AMP-dependent kinase (AMPK) signaling pathway. Our results showed that EAP water extract significantly inhibits ROS production, adipogenesis, and lipogenesis during differentiation of 3T3-L1 preadipocytes. In addition, EAP decreased mRNA and protein levels of proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα). Moreover, EAP suppressed mRNA expressions of fatty acid synthase (FAS), lipoprotein lipase (LPL), adipocyte protein 2 (aP2) in a dose-dependent manner. Whereas, EAP upregulated adiponectin expression, phosphorylation levels of AMPK and carnitine palmitoyltransferase 1 (CPT-1) protein level during differentiation of 3T3-L1 preadipocytes. These results suggest that EAP water extract can exert ROS-linked anti-obesity effect through the mechanism that might involve inhibition of ROS production, adipogenesis and lipogenesis via an activating AMPK signaling pathway.

scholarly journals Abrus agglutinin targets cancer stem-like cells by eliminating self-renewal capacity accompanied with apoptosis in oral squamous cell carcinoma

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770163 ◽  
Author(s):  
Niharika Sinha ◽  
Prashanta Kumar Panda ◽  
Prajna Paramita Naik ◽  
Tapas K Maiti ◽  
Sujit K Bhutia
Keyword(s):  
Reactive Oxygen Species ◽  
Oral Cancer ◽  
Caspase 3 ◽  
Glycogen Synthase ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Self Renewal ◽  
Fadu Cells ◽  
Dose Dependent

The accumulating evidences show that Abrus agglutinin, a plant lectin, displays a broad range of anticancer activity including cancer-specific induction of apoptosis; however, the underlying molecular mechanism of Abrus agglutinin–induced oral cancer stem cell elimination remains elusive. Our data documented that Abrus agglutinin effectively downregulated the CD44+ expression with the increased CD44− population in different oral cancer cells. After 24-h Abrus agglutinin treatment, FaDu cells were quantified for orosphere formation in ultra-low attachment plates and data showed that Abrus agglutinin inhibited the number and size of orosphere in a dose-dependent manner in FaDu cells. Furthermore, Abrus agglutinin hindered the plasticity of FaDu orospheres as supported by reduced sphere formation and downregulated the self-renewal property via inhibition of Wnt-β-catenin signaling pathway. Introduction of LiCl, a glycogen synthase kinase 3β inhibitor, rescued the Abrus agglutinin–stimulated inhibition of β-catenin and phosphorylated glycogen synthase kinase 3β in FaDu cell–derived orospheres confirming importance of Wnt signaling in Abrus agglutinin–mediated inhibition of stemness. In this connection, our data showed that Abrus agglutinin restrained proliferation and induced apoptosis in FaDu-derived cancer stem cells in dose-dependent manner. Moreover, western blot data demonstrated that Abrus agglutinin increased the Bax/Bcl-2 ratio with activation of poly(adenosine diphosphate–ribose) polymerase and caspase-3 favoring apoptosis induction in orospheres. Abrus agglutinin induced reactive oxygen species accumulation in orospheres and pretreatment of N-acetyl cysteine, and a reactive oxygen species scavenger inhibited Abrus agglutinin–mediated caspase-3 activity and β-catenin expression indicating reactive oxygen species as a principal regulator of Wnt signaling and apoptosis. In conclusion, Abrus agglutinin has a potential role as an integrative therapeutic approach for combating oral cancer through targeting self-renewability of orospheres via reactive oxygen species–mediated apoptosis.

scholarly journals Imbalanced Production of Reactive Oxygen Species and Mitochondrial Antioxidant SOD2 in Fabry Disease-Specific Human Induced Pluripotent Stem Cell-Differentiated Vascular Endothelial Cells

2017 ◽  
Vol 26 (3) ◽  
pp. 513-527 ◽  
Author(s):  
Wei-Lien Tseng ◽  
Shih-Jie Chou ◽  
Huai-Chih Chiang ◽  
Mong-Lien Wang ◽  
Chian-Shiu Chien ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Fabry Disease ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Ros Production ◽  
Oxygen Species ◽  
Ampk Activity ◽  
Induced Pluripotent

Fabry disease (FD) is an X-linked inherited lysosomal storage disease caused by α-galactosidase A (GLA) deficiency. Progressive intracellular accumulation of globotriaosylceramide (Gb3) is considered to be pathogenically responsible for the phenotype variability of FD that causes cardiovascular dysfunction; however, molecular mechanisms underlying the impairment of FD-associated cardiovascular tissues remain unclear. In this study, we reprogrammed human induced pluripotent stem cells (hiPSCs) from peripheral blood cells of patients with FD (FD-iPSCs); subsequently differentiated them into vascular endothelial-like cells (FD-ECs) expressing CD31, VE-cadherin, and vWF; and investigated their ability to form vascular tube-like structures. FD-ECs recapitulated the FD pathophysiological phenotype exhibiting intracellular Gb3 accumulation under a transmission electron microscope. Moreover, compared with healthy control iPSC-derived endothelial cells (NC-ECs), reactive oxygen species (ROS) production considerably increased in FD-ECs. Microarray analysis was performed to explore the possible mechanism underlying Gb3 accumulation-induced ROS production in FD-ECs. Our results revealed that superoxide dismutase 2 (SOD2), a mitochondrial antioxidant, was significantly downregulated in FD-ECs. Compared with NC-ECs, AMPK activity was significantly enhanced in FD-ECs. Furthermore, to investigate the role of Gb3 in these effects, human umbilical vein endothelial cells (HUVECs) were treated with Gb3. After Gb3 treatment, we observed that SOD2 expression was suppressed and AMPK activity was enhanced in a dose-dependent manner. Collectively, our results indicate that excess accumulation of Gb3 suppressed SOD2 expression, increased ROS production, enhanced AMPK activation, and finally caused vascular endothelial dysfunction. Our findings suggest that dysregulated mitochondrial ROS may be a potential target for treating FD.

Melatonin reduces UV-induced reactive oxygen species in a dose-dependent manner in IL-3-stimulated leukocytes

2001 ◽  
Vol 31 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Tobias W. Fischer ◽  
Georg Scholz ◽  
Brunhilde Knöll ◽  
Uta-Christina Hipler ◽  
Peter Elsner
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Dose Dependent

Reactive oxygen species and mitochondrial membrane potential are modulated during CDDP-induced apoptosis in EC-109 cellsThis paper is one of a selection of papers in this Special Issue, entitled International Symposium on Recent Advances in Molecular, Clinical, and Social Medicine, and has undergone the Journal's usual peer-review process.

2007 ◽  
Vol 85 (2) ◽  
pp. 265-271 ◽  
Author(s):  
Xu-Bin Jing ◽  
Xian-Bin Cai ◽  
Hui Hu ◽  
Su-Zuan Chen ◽  
Bin-Ming Chen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Peer Review Process ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Apoptotic Pathway ◽  
Highly Active ◽  
Inhibition Of Growth ◽  
Induced Apoptosis ◽  
Dose Dependent

cis-Diamminedichloroplatinum (CDDP), commonly know as cisplatin, is a well known DNA-damaging agent, which is highly active in suppressing the proliferation of tumor cells. However, it is not clear that CDDP can induce growth inhibition of esophagus cancer cells. Using the cell line EC-109 from the esophagus, we found that CDDP would induce apoptotic responses. The addition of CDDP to cells led to the inhibition of growth in a time- and dose-dependent manner. CDDP generated reactive oxygen species (ROSs) in cells, which brought about a reduction in the intracellular mitochondrial transmembrane potential (Δψm), leading to apoptosis. Our findings demonstrate that ROSs, and the resulting oxidative stress, play a pivotal role in apoptosis. Preincubation of EC-109 cells with the hydrogen-peroxide-scavenging enzyme catalase partially inhibited the following: (i) the production of ROS; (ii) the disruption of the Δψm; and (iii) apoptosis. These results indicate that the enhancement of the generation of ROS and the disruption of Δψm are events involved in the apoptotic pathway of EC-109 induced by CDDP.

scholarly journals Reactive Oxygen Species-Mediated Autophagy by Ursolic Acid Inhibits Growth and Metastasis of Esophageal Cancer Cells

2020 ◽  
Vol 21 (24) ◽  
pp. 9409
Author(s):  
Na-Ri Lee ◽  
Ruo Yu Meng ◽  
So-Young Rah ◽  
Hua Jin ◽  
Navin Ray ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Viability ◽  
Ursolic Acid ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Cell Viability Assay ◽  
Protein Levels ◽  
Lc3 Puncta ◽  
Dose Dependent

Ursolic acid (UA) possesses various pharmacological activities, such as antitumorigenic and anti-inflammatory effects. In the present study, we investigated the mechanisms underlying the effects of UA against esophageal squamous cell carcinoma (ESCC) (TE-8 cells and TE-12 cells). The cell viability assay showed that UA decreased the viability of ESCC in a dose-dependent manner. In the soft agar colony formation assay, the colony numbers and size were reduced in a dose-dependent manner after UA treatment. UA caused the accumulation of vacuoles and LC3 puncta, a marker of autophagosome, in a dose-dependent manner. Autophagy induction was confirmed by measuring the expression levels of LC3 and p62 protein in ESCC cells. UA increased LC3-II protein levels and decreased p62 levels in ESCC cells. When autophagy was hampered using 3-methyladenine (3-MA), the effect of UA on cell viability was reversed. UA also significantly inhibited protein kinase B (Akt) activation and increased p-Akt expression in a dose-dependent manner in ESCC cells. Accumulated LC3 puncta by UA was reversed after wortmannin treatment. LC3-II protein levels were also decreased after treatment with Akt inhibitor and wortmannin. Moreover, UA treatment increased cellular reactive oxygen species (ROS) levels in ESCC in a time- and dose-dependent manner. Diphenyleneiodonium (an ROS production inhibitor) blocked the ROS and UA induced accumulation of LC3-II levels in ESCC cells, suggesting that UA-induced cell death and autophagy are mediated by ROS. Therefore, our data indicate that UA inhibits the growth of ESCC cells by inducing ROS-dependent autophagy.

scholarly journals Andrographolide, isolated from Andrographis paniculata, induces apoptosis in monocytic leukemia and multiple myeloma cells via augmentation of reactive oxygen species production

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 542
Author(s):  
Hiroki Doi ◽  
Taei Matsui ◽  
Johannes M. Dijkstra ◽  
Atsushi Ogasawara ◽  
Yuki Higashimoto ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Multiple Myeloma ◽  
Cell Line ◽  
Reactive Oxygen ◽  
Andrographis Paniculata ◽  
Dependent Manner ◽  
Ros Production ◽  
Oxygen Species ◽  
High Toxicity ◽  
Monocytic Leukemia

Background: Andrographolide (Andro) is a diterpenoid component of the plant Andrographis paniculata that is known for its anti-tumor activity against a variety of cancer cells.   Methods: We studied the effects of Andro on the viability of the human leukemia monocytic cell line THP-1 and the human multiple myeloma cell line H929. Andro was compared with cytosine arabinoside (Ara-C) and vincristine (VCR), which are well-established therapeutics against hematopoietic tumors. The importance of reactive oxygen species (ROS) production for the toxicity of each agent was investigated by using an inhibitor of ROS production, N-acetyl-L-cysteine (NAC).    Results:  Andro reduced the viability of THP-1 and H929 in a dose-dependent manner. H929 viability was highly susceptible to Andro, although only slightly susceptible to Ara-C. The agents Andro, Ara-C, and VCR each induced apoptosis, as shown by cellular shrinkage, DNA fragmentation, and increases in annexin V-binding, caspase-3/7 activity, ROS production, and mitochondrial membrane depolarization. Whereas Ara-C and VCR increased the percentages of cells in the G0/G1 and G2/M phases, respectively, Andro showed little or no detectable effect on cell cycle progression. The apoptotic activities of Andro were largely suppressed by NAC, an inhibitor of ROS production, whereas NAC hardly affected the apoptotic activities of Ara-C and VCR.  Conclusions: Andro induces ROS-dependent apoptosis in monocytic leukemia THP-1 and multiple myeloma H929 cells, underlining its potential as a therapeutic agent for treating hematopoietic tumors. The high toxicity for (thus forming: The high toxicity for H929 cells, by a mechanism that is different from that of Ara-C and VCR, is encouraging for further studies on the use of Andro against multiple myeloma.) H929 cells, by a mechanism that is different from that of Ara-C and VCR, is encouraging for further studies on the use of Andro against multiple myeloma.

scholarly journals Trichomonas vaginalis Induces SiHa Cell Apoptosis by NF-κB Inactivation via Reactive Oxygen Species

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Juan-Hua Quan ◽  
Byung-Hun Kang ◽  
Jung-Bo Yang ◽  
Yun-Ee Rhee ◽  
Heung-Tae Noh ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Fragmentation ◽  
Trichomonas Vaginalis ◽  
Reactive Oxygen ◽  
Host Cells ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Ros Production ◽  
Oxygen Species ◽  
Siha Cells

Trichomonas vaginalis induces apoptosis in host cells through various mechanisms; however, little is known about the relationship between apoptosis, reactive oxygen species (ROS), and NF-κB signaling pathways in the cervical mucosal epithelium. Here, we evaluated apoptotic events, ROS production, and NF-κB activity in T. vaginalis-treated cervical mucosal epithelial SiHa cells, with or without specific inhibitors, using fluorescence microscopy, DNA fragmentation assays, subcellular fractionation, western blotting, and luciferase reporter assay. SiHa cells treated with live T. vaginalis at a multiplicity of infection of 5 (MOI 5) for 4 h produced intracellular and mitochondrial ROS in a parasite-load-dependent manner. Incubation with T. vaginalis caused DNA fragmentation, cleavage of caspase 3 and PARP, and release of cytochrome c into the cytoplasm. T. vaginalis-treated SiHa cells showed transient early NF-κB p65 nuclear translocation, which dramatically dropped at 4 h after treatment. Suppression of NF-κB activity was dependent on parasite burden. However, treatment with the ROS scavenger, N-acetyl-C-cysteine (NAC), reversed the effect of T. vaginalis on apoptosis and NF-κB inactivation in SiHa cells. Taken together, T. vaginalis induces apoptosis in human cervical mucosal epithelial cells by parasite-dose-dependent ROS production through an NF-κB-regulated, mitochondria-mediated pathway.

scholarly journals Internal Thiols and Reactive Oxygen Species in Candidacidal Activity Exerted by an N-Terminal Peptide of Human Lactoferrin

2002 ◽  
Vol 46 (6) ◽  
pp. 1634-1639 ◽  
Author(s):  
Antonella Lupetti ◽  
Akke Paulusma-Annema ◽  
Sonia Senesi ◽  
Mario Campa ◽  
Jaap T. van Dissel ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Extracellular Atp ◽  
Human Lactoferrin ◽  
Mitochondrial Activity ◽  
Dependent Manner ◽  
Ros Production ◽  
Oxygen Species ◽  
Irreversible Inhibitor ◽  
Ros Scavenger

ABSTRACT We previously showed that the energized mitochondrion and extracellular ATP are essential for the candidacidal activity of the N-terminal peptide of human lactoferrin, subsequently referred to as hLF(1-11). The present study focuses on the involvement of internal thiols and reactive oxygen species (ROS) in the candidacidal activity exerted by hLF(1-11). Our results reveal that hLF(1-11) reduced the internal thiol level of Candida albicans by 20%. In agreement, N-acetyl-l-cysteine (NAC), which is a precursor of glutathione and an ROS scavenger, inhibited the candidacidal activity of hLF(1-11). In addition, azodicarboxylic acid bis(N,N-dimethylamide) (diamide), which oxidizes internal thiols, was candidacidal. Furthermore, hLF(1-11) increased the level of ROS production by C. albicans in a dose-dependent manner, and a correlation between ROS production and candidacidal activity was found. 6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox), which is an ROS scavenger, partially inhibited the hLF(1-11)-induced, but not the diamide-triggered, candidacidal activity. It is of interest that hLF(1-11) and diamide acted synergistically in killing C. albicans and in ROS production. In agreement, oxidized ATP, an irreversible inhibitor of extracellular ATP receptors, partially blocked the hLF(1-11)-induced, but not the diamide-triggered, candidacidal activity. Finally, the hLF(1-11)-induced activation of mitochondria was inhibited by NAC, indicating that internal thiols and ROS affect mitochondrial activity. Therefore, the candidacidal activity of hLF(1-11) involves both generation of ROS and reduction of internal thiols.

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