scholarly journals Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro by inhibiting the p53-dependent mitochondrial apoptotic pathway

2016 ◽  
Vol 37 (5) ◽  
pp. 664-673 ◽  
Author(s):  
Yoon-Jin Lee ◽  
Soo A Kim ◽  
Sang-Han Lee
Keyword(s):  
Human Chondrocytes ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway ◽  
Induced Apoptosis

Role of Mitochondrial Apoptotic Pathway in Disulfiram/Copper Mixture-Induced Cell Apoptosis in Human B-Lineage Acute Lymphoblastic Leukemia in Vitro

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4920-4920
Author(s):  
Bing Xu ◽  
Manman Deng ◽  
Zhiwu Jiang ◽  
Jie Li ◽  
Kai Chen ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Dependent Manner ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway ◽  
B Lineage ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
Cytotoxic Mechanism

Abstract Backgrounds: The long term prognosis of adult B-lineage acute lymphoblastic leukemia (B-ALL) is poor when compared with pediatric B-ALL. The current therapeutic regimen for adult B-ALL often results in refractory and relapsing diseases. Therefore, it is urgently needed to explore novel approaches to treat adult B-ALL. Disulfiram (DS) has been used clinically as a safe anti-alcoholism drug for over 6 decades. Recent studies demonstrated that disulfiram/cooper mixture (DS/Cu) was cytotoxic to multiple solid cancers, but its effects on B-ALL cells are still unclear. Moreover, the molecular mechanism of the cytotoxicity of DS/Cu to tumor cells was poorly defined. In this study, we investigated the effects of DS/Cu on B-ALL cells in vitro and its related cytotoxic mechanism. Results: Firstly, CCK8 assay indicated that DS/Cu markedly inhibited Nalm6 cell proliferation in a dose-dependent manner. Secondly, colony-forming assay showed that DS/Cu also abolished the clonogenicity of Nalm6 cells (P<0.001). Thirdly, FACS analyses revealed that DS/Cu mixture could induce apoptosis of Nalm6 cells, as well as primary B-ALL cells (n=16) in a dose-dependent manner. We additionally analyzed the relationship between clinical characteristics of B-ALL patients, including age, WBC counts, immunophenotype, cytogenetics, risk stratification and Ph chromosome, with the efficacy of DS/Cu on B-ALL cells. The apoptosis isolated from pro-B and cytogenetic abnormality B-ALL pastients was higher. Therefore, our results demonstrated that DS/Cu mixture could induce significant cytotoxicity against B-ALL cells in vitro. To decipher the cytotoxic mechanism of DS/Cu mixture, JC-1 staining was done and the results showed that DS/Cu mixture could significantly reduce the mitochondrial membrane potential in Nalm6 cells (P<0.01) and 7 cases of primary B-ALL cells (P<0.05). Consistently, Western Blot analysis showed that DS/Cu induced B-ALL cell apoptosis by down-regulating the expression of anti-apoptotic protein Bcl2 and Bcl-XL, as well as activating caspase-3 and its substrate PARP. Hence, our results indicated that DS/Cu induced apoptosis of B-ALL cells at least partly through the intrinsic mitochondrial apoptotic pathway. Conclusion: Our results demonstrated that DS/Cu not only significantly inhibit proliferation and clonogenicity, but also induce apoptosis of B-ALL cells in vitro.The mitochondrial apoptotic pathway might be the molecular mechanism of DS/Cu-induced apoptosis of B-ALL cells. Disclosures No relevant conflicts of interest to declare.

MicroRNA-15b enhances hypoxia/reoxygenation-induced apoptosis of cardiomyocytes via a mitochondrial apoptotic pathway

APOPTOSIS ◽  
2013 ◽  
Vol 19 (1) ◽  
pp. 19-29 ◽  
Author(s):  
Lifeng Liu ◽  
Guoming Zhang ◽  
Zhuo Liang ◽  
Xiuhua Liu ◽  
Tiande Li ◽  
...  
Keyword(s):  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway ◽  
Induced Apoptosis ◽  
Hypoxia Reoxygenation

scholarly journals Apigenin Suppresses Angiogenesis by Inhibiting Tube Formation and Inducing Apoptosis

2016 ◽  
Vol 11 (10) ◽  
pp. 1934578X1601101
Author(s):  
Hyun Ju Kim ◽  
Mok-Ryeon Ahn
Keyword(s):  
Umbilical Vein ◽  
Chorioallantoic Membrane ◽  
Tube Formation ◽  
Anticancer Activities ◽  
Apoptotic Pathway ◽  
Inhibition Of Angiogenesis ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

Apigenin has been reported to exert angiogenic and anticancer activities in vitro. The mechanism of inhibition of angiogenesis by apigenin, however, has not been well-established. In this study, we investigated whether apigenin not only inhibited tube formation but also induced apoptosis in human umbilical vein endothelial cells (HUVECs). Furthermore, strong antiangiogenic activity of apigenin was observed in the in vivo assay using chick embryo chorioallantoic membrane (CAM). We also analyzed changes in survival signals and the apoptotic pathway through Western blotting. The results indicate that apigenin exerts its antiangiogenic effects through induction of endothelial apoptosis.

scholarly journals C-phycocyanin from Limnothrix Species KNUA002 Alleviates Cisplatin-Induced Ototoxicity by Blocking the Mitochondrial Apoptotic Pathway in Auditory Cells

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 235 ◽  
Author(s):  
Ye-Ri Kim ◽  
Jeong-Mi Do ◽  
Kyung Hee Kim ◽  
Alexandra R. Stoica ◽  
Seung-Woo Jo ◽  
...  
Keyword(s):  
Organ Of Corti ◽  
Experimental Models ◽  
Common Side Effect ◽  
Anticancer Activities ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway ◽  
Anticancer Chemotherapy ◽  
Ros Accumulation

Ototoxicity, or adverse pharmacological effects on the inner ear or auditory nerve, is a common side effect of cisplatin, a platinum-based drug widely used in anticancer chemotherapy. Although the incidence of ototoxicity is high among patients that receive cisplatin therapy, there is currently no effective treatment for it. The generation of excessive reactive oxygen species (ROS) is considered to be the major cause of cisplatin-induced ototoxicity. C-phycocyanin (C-PC), a blue phycobiliprotein found in cyanobacteria and red algae, has antioxidant and anticancer activities in different experimental models in vitro and in vivo. Thus, we tested the ability of C-PC from Limnothrix sp. KNUA002 to protect auditory cells from cisplatin-induced ototoxicity in vitro. Pretreatment with C-PC from Limnothrix sp. KNUA002 inhibited apoptosis and protected mitochondrial function by preventing ROS accumulation in cisplatin-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, a mouse auditory cell line. Cisplatin increased the expression of Bax and reduced the expression of Bcl-2, which activate and inhibit, respectively, the mitochondrial apoptotic pathway in response to oxidative stress. Pretreatment with C-PC prior to cisplatin treatment caused the Bax and Bcl-2 levels to stay close to the levels in untreated control cells. Our results suggest that C-PC from Limnothrix sp. KNUA002 protects cells against cisplatin-induced cytotoxicity by inhibiting the mitochondrial apoptotic pathway.

scholarly journals Ginsenoside Rb1 Protects Neonatal Rat Cardiomyocytes from Hypoxia/Ischemia Induced Apoptosis and Inhibits Activation of the Mitochondrial Apoptotic Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Xu Yan ◽  
Jinwen Tian ◽  
Hongjin Wu ◽  
Yuna Liu ◽  
Jianxun Ren ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Neonatal Rat ◽  
Ginsenoside Rb1 ◽  
Caspase 9 ◽  
Apoptotic Pathway ◽  
Rat Cardiomyocytes ◽  
Mitochondrial Apoptotic Pathway ◽  
Neonatal Rat Cardiomyocytes ◽  
Hypoxia Ischemia

Aim. To investigate the effect of Ginsenoside Rb1 (GS-Rb1) on hypoxia/ischemia (H/I) injury in cardiomyocytesin vitroand the mitochondrial apoptotic pathway mediated mechanism.Methods. Neonatal rat cardiomyocytes (NRCMs) for the H/I groups were kept in DMEM without glucose and serum, and were placed into a hypoxic jar for 24 h. GS-Rb1 at concentrations from 2.5 to 40 µM was given during hypoxic period for 24 h. NRCMs injury was determined by MTT and lactate dehydrogenase (LDH) leakage assay. Cell apoptosis, ROS accumulation, and mitochondrial membrane potential (MMP) were assessed by flow cytometry. Cytosolic translocation of mitochondrial cytochrome c and Bcl-2 family proteins were determined by Western blot. Caspase-3 and caspase-9 activities were determined by the assay kit.Results. GS-Rb1 significantly reduced cell death and LDH leakage induced by H/I. It also reduced H/I induced NRCMs apoptosis induced by H/I, in accordance with a minimal reactive oxygen species (ROS) burst. Moreover, GS-Rb1 markedly decreased the translocation of cytochrome c from the mitochondria to the cytosol, increased the Bcl-2/ Bax ratio, and preserved mitochondrial transmembrane potential (ΔΨm). Its administration also inhibited activities of caspase-9 and caspase-3.Conclusion. Administration of GS-Rb1 during H/Iin vitrois involved in cardioprotection by inhibiting apoptosis, which may be due to inhibition of the mitochondrial apoptotic pathway.

Azacytidine Suppressors Autocrine IL-6 Secretion and Demonstrates In Vitro and In Vivo Activity Against Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1566-1566
Author(s):  
Tiffany Khong ◽  
Janelle Sharkey ◽  
Andrew Spencer
Keyword(s):  
Multiple Myeloma ◽  
Murine Model ◽  
Dna Methyltransferase ◽  
Myeloma Cell ◽  
Apoptotic Pathway ◽  
P16 Gene ◽  
Induced Apoptosis ◽  
The Impact

Abstract Azacytidine (AZA), a DNA methyltransferase inhibitor, has been shown to inhibit cell growth and induce apoptosis in some cancer cells. We determined the impact of AZA on a panel of human myeloma cell lines (HMCL); KMS 12PE, KMS 18, LP-1, NCI-H929, OPM-2, RPMI-8226 and U266 and in an in vivo murine model of multiple myeloma (5T33 model). Dose responsiveness to AZA was determined via MTS assays with a range of AZA doses (1–10mM) for 72 hours. FACS and cell cycle analysis were used to evaluate the profile of the cells after exposure to AZA for 72 hours. MTS assays demonstrated a dose and time dependent AZA-induced inhibition of HMCL viability with effective concentrations of AZA ranging from 1–10 mM. This was associated with accumulation of cells in the Go/G1 phase with decreasing number of cells in the S and G2/M phases. Western Blot analysis using antibodies against caspases 3,8,10, PARP, phospho-ERK, ERK, Stat3 and phospho -Stat3 were performed to help characterize the mechanism(s) of cell killing. Cleavage of caspases 3,8,10 and PARP within 24 hours of AZA treatment confirmed early AZA-induced HMCL apoptosis. phospho-ERK which was absent in untreated U266 appeared after 48 hours exposure to 5mM AZA. Similarly inhibitors of caspases 3,8 and 9 were used to determine which apoptotic pathway was being preferentially activated by AZA. Inhibitors of both caspase 3 and 9 effectively abrogated AZA-induced apoptosis in U266 and NCI-H929. In contrast caspase 8 inhibitor was less effective which is consistent with AZA acting via the mitochondrial apoptotic pathway. Reactivation of p16 gene by AZA-induced hypomethylation was assessed with methylation specific PCR. MSP-PCR of the p16 gene indicated a loss of methylation and up-regulated transcription after 48 hours treatment with 5 mM AZA. The level of IL-6 in conditioned media from U266 cells treated with AZA was determined by ELISA assay and demonstrated a rapid fall in autocrine IL-6 production. RT-PCR demonstrated rapid AZA-induced cessation of IL-6 transcription temporarily associated with the disappearance of upstream phospho -Stat3. Addition of exogenous IL-6 did not rescue U266 from AZA-induced apoptosis. AZA was also administered to a 5T33 murine model of multiple myeloma at increasing concentrations (1, 3, 10 mg/kg). At 10 mg/kg the median survival of vehicle versus AZA treated mice was 28 days versus 30+ days (p=0.003). These findings justify further evaluation of AZA as a potential therapeutic agent for multiple myeloma.

scholarly journals Enterovirus 71 2B Induces Cell Apoptosis by Directly Inducing the Conformational Activation of the Proapoptotic Protein Bax

2016 ◽  
Vol 90 (21) ◽  
pp. 9862-9877 ◽  
Author(s):  
Haolong Cong ◽  
Ning Du ◽  
Yang Yang ◽  
Lei Song ◽  
Wenliang Zhang ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Enterovirus 71 ◽  
Terminal Region ◽  
Ev71 Infection ◽  
Apoptotic Pathway ◽  
Hydrophobic Region ◽  
Mitochondrial Apoptotic Pathway ◽  
Proapoptotic Protein ◽  
2B Protein ◽  
Induced Apoptosis

ABSTRACTTo survive and replicate within a host, many viruses have evolved strategies that target crucial components within the apoptotic cascade, leading to either inhibition or induction of cell apoptosis. Enterovirus 71 (EV71) infections have been demonstrated to impact the mitochondrial apoptotic pathway and induce apoptosis in many cell lines. However, the detailed mechanism of EV71-induced apoptosis remains to be elucidated. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax. 2B recruited Bax to the mitochondria and induced Bax conformational activation. In addition, mitochondria isolated from 2B-expressing cells that were treated with a recombinant Bax showed increased Bax interaction and cytochromec(Cytc) release. Importantly, apoptosis in cells with either EV71 infection or 2B expression was dramatically reduced in Bax knockdown cells but not in Bak knockdown cells, suggesting that Bax played a pivotal role in EV71- or 2B-induced apoptosis. Further studies indicate that a hydrophobic region of 18 amino acids (aa) in the C-terminal region of 2B (aa 63 to 80) was responsible for the location of 2B in the mitochondria. A hydrophilic region of 14 aa in the N-terminal region of 2B was functional in Bax interaction and its subsequent activation. Moreover, overexpression of the antiapoptotic protein Bcl-XLabrogates 2B-induced release of Cytcand caspase activation. Therefore, this study provides direct evidence that EV71 2B induces cell apoptosis and impacts the mitochondrial apoptotic pathway by directly modulating the redistribution and activation of proapoptotic protein Bax.IMPORTANCEEV71 infections are usually accompanied by severe neurological complications. It has also been postulated that the induction of cell apoptosis resulting from tissue damage is a possible process of EV71-related pathogenesis. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax. This study provides evidence that EV71 induces cell apoptosis by modulating Bax activation and reveals important clues regarding the mechanism of Cytcrelease and mitochondrial permeabilization during EV71 infection.

scholarly journals Time Dependent Appearance of Selected Apoptotic Markers and Usefulness of Their Detection In vitro

2002 ◽  
Vol 45 (4) ◽  
pp. 135-144 ◽  
Author(s):  
Emil Rudolf ◽  
Miroslav Červinka
Keyword(s):  
Caspase 3 ◽  
Potassium Chromate ◽  
Experimental Setting ◽  
Apoptotic Pathway ◽  
Detection Systems ◽  
Chemically Induced ◽  
Cell Blebbing ◽  
Temporary Decrease ◽  
Induced Apoptosis

Many experiments have demonstrated that some cell lines are resistant to chemically induced apoptosis in vitro, and that apoptosis itself is far from being a homogenous phenomenon. Here we show that 10 μg/ml etoposide elicited only minor changes in Bowes human melanoma cells (temporary decrease in cell viability and proliferation, transient phospatidylserine externalization and caspase-3 activation), which weren’t clearly capable to start apoptotic pathway in the entire treated population. On the other hand, potassium chromate at concentration of 150 μg/ml executed cell death bearing some features of apoptosis (cell blebbing, caspase-3 activation and cytoskeletal changes) but lacking or showing weakly others (DNA fragmentation and phospatidylserine externalization). Our results suggest that in detecting apoptosis several faultproof detection systems are to be used to avoid misleading results and conclusions in each experimental setting.

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