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 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 ◽  
Monocytic Leukemia ◽  
Mitochondrial Membrane Depolarization

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. 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, reactive oxygen species (ROS) production, and mitochondrial membrane depolarization. The apoptotic activities of Andro were largely suppressed by N-acetyl-L-cysteine (NAC), an inhibitor of ROS production, whereas NAC hardly affected the apoptotic activities of Ara-C and VCR. Furthermore, 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. 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. Notably, the high sensitivity of H929 cells is encouraging for further studies on the use of Andro against multiple myeloma.

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 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.

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 P2X7 Receptor Activation Induces Reactive Oxygen Species Formation and Cell Death in Murine EOC13 Microglia

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Rachael Bartlett ◽  
Justin J. Yerbury ◽  
Ronald Sluyter
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cell Line ◽  
Purinergic Receptor ◽  
Reactive Oxygen ◽  
Receptor Activation ◽  
Organic Cations ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Ros Formation

The P2X7 purinergic receptor is a ligand-gated cation channel expressed on leukocytes including microglia. This study aimed to determine if P2X7 activation induces the uptake of organic cations, reactive oxygen species (ROS) formation, and death in the murine microglial EOC13 cell line. Using the murine macrophage J774 cell line as a positive control, RT-PCR, immunoblotting, and immunolabelling established the presence of P2X7 in EOC13 cells. A cytofluorometric assay demonstrated that the P2X7 agonists adenosine-5′-triphosphate (ATP) and 2′(3′)-O-(4-benzoylbenzoyl) ATP induced ethidium+or YO-PRO-12+uptake into both cell lines. ATP induced ethidium+uptake into EOC13 cells in a concentration-dependent manner, with an EC50of~130 μM. The P2X7 antagonists Brilliant Blue G, A438079, AZ10606120, and AZ11645373 inhibited ATP-induced cation uptake into EOC13 cells by 75–100%. A cytofluorometric assay demonstrated that P2X7 activation induced ROS formation in EOC13 cells, via a mechanism independent of Ca2+influx and K+efflux. Cytofluorometric measurements of Annexin-V binding and 7AAD uptake demonstrated that P2X7 activation induced EOC13 cell death. The ROS scavenger N-acetyl-L-cysteine impaired both P2X7-induced EOC13 ROS formation and cell death, suggesting that ROS mediate P2X7-induced EOC13 death. In conclusion, P2X7 activation induces the uptake of organic cations, ROS formation, and death in EOC13 microglia.

scholarly journals Generation of Reactive Oxygen Species during Apoptosis Induced by DNA-Damaging Agents and/or Histone Deacetylase Inhibitors

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Barbora Brodská ◽  
Aleš Holoubek
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Line ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Actinomycin D ◽  
Reactive Oxygen ◽  
Leukemia Cell Line ◽  
Ros Production ◽  
Oxygen Species ◽  
Dna Damaging Agents

Reactive oxygen species play an important role in the process of apoptosis in many cell types. In this paper, we analyzed the role of ROS in DNA-damaging agents (actinomycin D or decitabine), which induced apoptosis of leukemia cell line CML-T1 and normal peripheral blood lymphocytes (PBL). The possibility of synergism with histone deacetylase inhibitors butyrate or SAHA is also reported. We found that in cancer cell line, ROS production significantly contributed to apoptosis triggering, while in normal lymphocytes treated by cytostatic or cytotoxic drugs, necrosis as well as apoptosis occurred and large heterogeneity of ROS production was measured. Combined treatment with histone deacetylase inhibitor did not potentiate actinomycin D action, whereas combination of decitabine and SAHA brought synergistic ROS generation and apoptotic features in CML cell line. Appropriate decrease of cell viability indicated promising therapeutic potential of this combination in CML, but side effects on normal PBL should be taken into attention.

scholarly journals Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cells

2005 ◽  
Vol 289 (5) ◽  
pp. L834-L841 ◽  
Author(s):  
Kenneth E. Chapman ◽  
Scott E. Sinclair ◽  
Daming Zhuang ◽  
Aviv Hassid ◽  
Leena P. Desai ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Epithelial Cells ◽  
Cell Line ◽  
Primary Cultures ◽  
Reactive Oxygen ◽  
Lung Epithelial Cells ◽  
Alveolar Type ◽  
Ros Production ◽  
Oxygen Species ◽  
Type Ii

Overdistention of lung tissue during mechanical ventilation may be one of the factors that initiates ventilator-induced lung injury (VILI). We hypothesized that cyclic mechanical stretch (CMS) of the lung epithelium is involved in the early events of VILI through the production of reactive oxygen species (ROS). Cultures of an immortalized human airway epithelial cell line (16HBE), a human alveolar type II cell line (A549), and primary cultures of rat alveolar type II cells were cyclically stretched, and the production of superoxide (O2−) was measured by dihydroethidium fluorescence. CMS stimulated increased production of O2− after 2 h in each type of cell. 16HBE cells exhibited no significant stimulation of ROS before 2 h of CMS (20% strain, 30 cycles/min), and ROS production returned to control levels after 24 h. Oxidation of glutathione (GSH), a cellular antioxidant, increased with CMS as measured by a decrease in the ratio of the reduced GSH level to the oxidized GSH level. Strain levels of 10% did not increase O2− production in 16HBE cells, whereas 15, 20, and 30% significantly increased generation of O2−. Rotenone, a mitochondrial complex I inhibitor, partially abrogated the stretch-induced generation of O2− after 2 h CMS in 16HBE cells. NADPH oxidase activity was increased after 2 h of CMS, contributing to the production of O2−. Increased ROS production in lung epithelial cells in response to elevated stretch may contribute to the onset of VILI.

Regulation of reactive oxygen species (ROS) production by C18 fatty acids in Jurkat and Raji cells

2005 ◽  
Vol 108 (3) ◽  
pp. 245-253 ◽  
Author(s):  
Maria F. CURY-BOAVENTURA ◽  
Rui CURI
Keyword(s):  
Reactive Oxygen Species ◽  
Fatty Acids ◽  
Olive Oil ◽  
Cell Line ◽  
B Lymphocyte ◽  
Reactive Oxygen ◽  
Jurkat Cells ◽  
Ros Production ◽  
Oxygen Species ◽  
Raji Cells

In the present study, the effects of C18 fatty acids with different numbers of double bonds, SA (stearic acid; C18:0), OA (oleic acid; C18:1), LA (linoleic acid; C18:2) and γ-LNA (γ-linolenic acid; C18:3), on ROS (reactive oxygen species) production by Jurkat (a human T-lymphocyte-derived cell line) and Raji (a human B-lymphocyte-derived cell line) cells were investigated. ROS production was determined by NBT (Nitro Blue Tetrazolium) reduction (intracellular and extracellular ROS production) and by dihydroethidium oxidation using flow cytometry (intracellular ROS production). The effectiveness on ROS production was γ-LNA<SA<OA<LA in Jurkat cells and SA<γ-LNA<OA<LA in Raji cells. LA (found in corn, soya bean and sunflower oils) was more potent than OA (found in olive oil) in stimulating ROS production in both Raji and Jurkat cells. The lower ROS production by OA compared with LA may be one of the benefits of olive oil consumption. As SA and γ-LNA acids had little or no effect, further studies on the site of ROS production in these cells were carried out with OA and LA only. Activation of NADPH oxidase via PKC (protein kinase C) was found to be the major mechanism of ROS production induced by OA and LA in Jurkat and Raji cells.

Motexafin gadolinium generates reactive oxygen species and induces apoptosis in sensitive and highly resistant multiple myeloma cells

Blood ◽  
2005 ◽  
Vol 105 (3) ◽  
pp. 1265-1273 ◽  
Author(s):  
Andrew M. Evens ◽  
Philip Lecane ◽  
Darren Magda ◽  
Sheila Prachand ◽  
Seema Singhal ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Multiple Myeloma ◽  
Reactive Oxygen ◽  
Drug Uptake ◽  
Ros Production ◽  
Oxygen Species ◽  
Cellular Cytotoxicity ◽  
Motexafin Gadolinium ◽  
Inhibition Of Proliferation ◽  
Myeloma Cells

AbstractMotexafin gadolinium (MGd), an expanded porphyrin, is a tumor-selective redox-mediator that reacts with many intracellular reducing metabolites. Because redox mechanisms mediate apoptosis in multiple myeloma, we hypothesized that disruption of redox balance by MGd would result in cellular cytotoxicity in myeloma. We examined the effects of MGd on cellular cytotoxicity, apoptosis, reactive oxygen species (ROS) production, and intracellular drug uptake in dexamethasone-sensitive (C2E3), dexamethasone-resistant (1-310 and 1-414) chemotherapy-sensitive (8226-RPMI) and highly chemotherapy-resistant (DOX-10V) myeloma cells. We found complete inhibition of proliferation and cytotoxicity in each sensitive and resistant cell line with 24-hour exposure to clinically relevant concentrations of 50 μM MGd and 50 to 100 μM ascorbate, which was required for the effect. The mechanism of cytotoxicity was related to induction of apoptosis as demonstrated by alteration in mitochondrial membrane potential and elevated annexin V expression. This was accompanied by depletion of intracellular glutathione and increased ROS production. Moreover, catalase substantially abrogated MGd-induced cell death. Using fluorescence microscopy and flow cytometry, we found intracellular uptake of MGd and intracellular ROS production. MGd also induced apoptosis in fresh malignant cells from patients with multiple myeloma. These studies provide a rationale for clinical investigation of this novel redox-mediating agent in patients with multiple myeloma and related disorders.

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