Peroxisome Proliferator-Activated Receptor-γ Agonist Rosiglitazone– Induced Apoptosis in Leukemia K562 Cells and Its Mechanisms of Action

2009 ◽  
Vol 28 (2) ◽  
pp. 123-131 ◽  
Author(s):  
Jia-Jun Liu ◽  
Ting Hu ◽  
Xiang-Yuan Wu ◽  
Chun-Zhi Wang ◽  
Yan Xu ◽  
...  
Keyword(s):  
Caspase 3 ◽  
K562 Cells ◽  
Telomerase Activity ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Apoptotic Protein ◽  
Induced Apoptosis ◽  
Dose Dependent

This study investigates the ability of a synthetic PPAR-γ agonist, rosiglitazone (RGZ), to induce apoptosis in leukemia K562 cells. The results revealed that RGZ (>40 mmol/L) inhibits the growth of K562 cells and causes apoptosis in a time and dose-dependent manner. Apoptosis is observed clearly by Hoechst 33258 staining. Western blotting analysis demonstrates the cleavage of caspase-3 zymogen protein with the appearance of its 17-kD subunit and a dose-dependent cleavage of poly (ADP-ribose) polymerase. Furthermore, RGZ treatment down-regulates anti-apoptotic protein Bcl-2 and up-regulates pro-apoptotic protein Bax in a dosedependent manner after the cells are treated for 48 hours. Telomerase activity is decreased concurrently in a dosedependent manner. We therefore conclude that RGZ induces apoptosis in K562 cells in vitro, and that RGZ-induced apoptosis in K562 cells is highly correlated with activation of caspase-3, decreasing telomerase activity, down-regulation of the anti-apoptotic protein Bcl-2, and up-regulation of the pro-apoptotic protein Bax.

PAEDERUS ALFIERI EXTRACT INDUCES APOPTOSIS IN HUMAN MYELOID LEUKEMIA K562 CELLS

2016 ◽  
Vol 10 (1) ◽  
pp. 72
Author(s):  
Amer Mohamed ◽  
Osama Rakha
Keyword(s):  
Myeloid Leukemia ◽  
Caspase 3 ◽  
Insect Pests ◽  
Flow Cytometric Analysis ◽  
K562 Cells ◽  
Akt Pathway ◽  
Dependent Manner ◽  
Proliferative Effect ◽  
Induced Apoptosis ◽  
Dose Dependent

ABSTRACTObjective: The rove beetle Paederus alfieri Koch. (Coleoptera: Staphylinidae) is well-known among natural enemies in Egypt as an important predatorof agricultural insect pests, it used as an essential agent in the integrated pest management programs. Recent studies have revealed that Paederus mayhave anti-proliferative effect; however, its mechanisms remain unclear. The aim of the present study is to investigate the anticancer effect of P. alfieriextract (PAE) on K562 human myeloid leukemia cancer cells and elucidation of its mechanism.Methods: Human myeloid leukemia K562 cells were treated with PAE at different concentrations. Cell proliferation was measured using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was evaluated using flow cytometry analysis. The expressions ofBcl-2, Bax, active caspase-3, t-Akt, and p-Akt were evaluated by western blotting.Results: PAE has a dose-dependent antiproliferative effect against K562 cells. The half maximal inhibitory concentration was estimated as212±2.3 ng/ml. Flow cytometric analysis showed that PAE induces apoptosis in a dose-dependent manner in K562 cells. We also investigated themolecular mechanism of PAE-induced apoptosis. PAE downregulated Bcl-2 and upregulated Bax and cleaved caspase-3 proteins. Furthermore, thelevels of p-Akt are dose-dependently decreased in response to PAE, whereas the total Akt protein levels remained constant during PAE treatment.Conclusion: Taken together PAE-induced apoptosis in human myeloid leukemia K562 cells by modulating PI3K/Akt pathway. Our findings suggestthat may be PAE is a good extract for developing anticancer drugs for human myeloid leukemia cancer treatment.Keywords: Paederus alfieri, Pederin, K562, Apoptosis, PI3K/Akt pathway.

Berbamine-Induced Apoptosis in Human Leukemia K562 Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4234-4234
Author(s):  
Xiaoying Zhao ◽  
Lei Xu ◽  
Dong Wu ◽  
Rongzhen Xu
Keyword(s):  
Flow Cytometry ◽  
Cell Proliferation ◽  
Caspase 3 ◽  
K562 Cells ◽  
Human Leukemia ◽  
Dependent Manner ◽  
Flow Cytometry Assay ◽  
Transcript Levels ◽  
Induced Apoptosis ◽  
Dose Dependent

Abstract Purpose: To investigate apoptosis-inducing effects of Berbamine on human leukemia cells and to explore the underlying mechanism. Materials and methods: Berbamine was dissolved in 0.9% sodium chloride to an initial concentration of 1mg/ml and subsequently diluted to desired concentrations with cell culture medium. MTT was used to examine the effect of Berbamine on cell proliferation of K562 cells. Characteristic cellular morphological changes were used as indicators of apoptosis in K562 cells while the rate of apoptosis was measured by flow cytometry assay. Expression levels of apoptosis related genes bcl-2 and bax were determined by RT-PCR and the levels of bcr/abl were evaluated by nested-PCR. Levels of Caspase 3 were measured by flow cytometry assay. Results: Berbamine inhibited the cell proliferation significantly and in a dose-dependent manner in tested K562 cells. Its IC50 value was 5.23ug/ml. As determined by morphological observations and flow cytometry assay, Berbamine was able to induce apoptosis of K562 cells within 6 hours. The apoptosis rate of K562 was also dose-dependent. Steady-state transcript levels of bcr/abl decreased dramatically (half-quantity ratio from 1.284 to 0.506 within 72 hours following 8mg/ml Berbamine treatment. On the other hand, the protein levels of Caspase 3 surged from 18.36% to 38.25% (p<0.001) within 24 hours after treatment of 12mg/ml Berbamine. During the same period, no changes of bcl-2 or bax transcript levels were detected in the cells that were treated with 8mg/ml Berbamine. Conclusions: Our results suggest that Berbamine is a potent inhibitor of cell proliferation and a strong inducer of apoptosis in human K562 cells. The Berbamine-induced apoptosis pathway involves down regulation of bcr/abl and up regulation of Caspase 3 expressions. Neither bcl-2 nor bax plays substantial roles in Berbamine-induced K562 cell apoptosis.

Molecular Mechanism of Matrine-Induced Apoptosis in Leukemia K562 Cells

2006 ◽  
Vol 34 (06) ◽  
pp. 1095-1103 ◽  
Author(s):  
Xiao-Shan Liu ◽  
Jikai Jiang
Keyword(s):  
Cytochrome C ◽  
Caspase 3 ◽  
Chinese Herb ◽  
K562 Cells ◽  
Dependent Manner ◽  
Nih3t3 Cells ◽  
Proapoptotic Protein ◽  
General Caspase Inhibitor ◽  
Induced Apoptosis ◽  
Dose Dependent

Matrine, a low toxic alkaloid purified from the Chinese herb Kushen, has been reported to induce apoptosis in leukemia K562 cells. In this study, the mechanism underling this apoptotic event was investigated. Treatment of K562 cells with matrine resulted in inhibition of cell survival more significantly than treatment of non-cancer fibroblast NIH3T3 cells. When K562 cells were incubated with matrine in higher than 0.2 mg/ml doses for 48 hours, the apoptotic cells were increased and both poly (ADP-ribose) polymerase (PARP) and caspase-3 were cleaved in a dose dependent manner. General caspase inhibitor (z-VAD-fmk) or caspase-3 inhibitor (z-DEVD-fmk) almost completely suppressed matrine-induced apoptosis. In addition, matrine increased proapoptotic protein bax and caused the release of cytochrome C. Taken together, the results suggest that matrine induces a cytochrome C-mediated, caspase-dependent apoptosis.

scholarly journals Thrombospondin-1 Inhibits Angiogenesis and Promotes Follicular Atresia in a Novel in Vitro Angiogenesis Assay

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 1280-1289 ◽  
Author(s):  
Samantha A. Garside ◽  
Christopher R. Harlow ◽  
Stephen G. Hillier ◽  
Hamish M. Fraser ◽  
Fiona H. Thomas
Keyword(s):  
Granulosa Cells ◽  
Caspase 3 ◽  
Polycystic Ovary ◽  
Dependent Manner ◽  
Ovary Syndrome ◽  
Angiogenesis Assay ◽  
Thrombospondin 1 ◽  
In Vitro Angiogenesis ◽  
Dose Dependent

Thrombospondin-1 (TSP-1) is a putative antiangiogenic factor, but its role in regulating physiological angiogenesis is unclear. We have developed a novel in vitro angiogenesis assay to study the effect of TSP-1 on follicular angiogenesis and development. Intact preantral/early antral follicles dissected from 21-d-old rat ovaries were cultured for 6 d in the presence or absence of TSP-1. At the end of the culture period, angiogenic sprouting from the follicles was quantified using image analysis. Follicles were fixed and sectioned, and follicular apoptosis was assessed by immunohistochemistry for activated caspase-3 in granulosa cells. The results showed that TSP-1 inhibited follicular angiogenesis (P &lt; 0.01) and promoted follicular apoptosis (P &lt; 0.001) in a dose-dependent manner. To determine whether the proapoptotic activity of TSP-1 is mediated by direct effects on granulosa cells, isolated granulosa cells were cultured with TSP-1 (0, 10, 100, and 1000 ng/ml) for 48 h. Apoptosis was quantified using a luminescent caspase-3/7 assay. TSP-1 promoted apoptosis of granulosa cells in a dose-dependent manner (P &lt; 0.05), suggesting that TSP-1 can act independently of the angiogenesis pathway to promote follicular apoptosis. These results show that TSP-1 can both inhibit follicular angiogenesis and directly induce apoptosis of granulosa cells. As such, it may have potential as a therapeutic for abnormal ovarian angiogenesis and could facilitate the destruction of abnormal follicles observed in polycystic ovary syndrome.

scholarly journals Targeting the EZH2-PPAR Axis Is a Potential Therapeutic Pathway for Pancreatic Cancer

PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jilong Hu ◽  
Zhinan Zheng ◽  
Jia Lei ◽  
Yuxin Cao ◽  
Qiyun Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cyclin D1 ◽  
Caspase 3 ◽  
Synergistic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonist ◽  
Combined Use

Enhancer of zeste homolog 2 (EZH2) is abnormally highly expressed in pancreatic cancer (PC). However, it is not ideal to treat PC by inhibiting EZH2. This study reported that the combined use of pan-peroxisome proliferator-activated receptor (PPAR) agonist could significantly improve the anti-PC effect of EZH2 inhibitor. In vitro, PC cell lines PANC-1 and AsPC-1 were cultured, and MTT and flow cytometry were performed to observe the effects of pan-PPAR agonist bezafibrate and EZH2 selective inhibitor GSK126 on cell viability and apoptosis. In vivo, CDXs of PANC-1 and AsPC-1 were established to observe the effects of bezafibrate and GSK126 on bearing tumors. Western blotting was performed to detect the protein expressions of H3K27me3, β-catenin, p-β-catenin, cyclin D1, c-Myc, and cleaved caspase 3 in vitro and in vivo. The results showed that bezafibrate significantly improved the effects of GSK126 on proliferation inhibition and apoptosis promotion in vitro and the growth suppression of CDX tumors in vivo. It also significantly enhanced the effects of GSK126 on upregulating the expression level of p-β-catenin and that of cleaved caspase 3 in vitro and in vivo. In parallel, downregulation of the expression levels of H3K27me3, β-catenin, cyclin D1, and c-Myc was also observed in vitro or in vivo. These results suggest that the combination of bezafibrate and GSK126 has synergistic effects on PC, and the molecular mechanism may be related to the enhanced inhibition of the Wnt/β-catenin signaling pathway. We believe that targeting the EZH2-PPAR axis is a potential therapeutic pathway for PC.

scholarly journals Autophagy Inhibition Enhances Apoptosis Induced by Dioscin in Huh7 Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Ming-Ju Hsieh ◽  
Shun-Fa Yang ◽  
Yih-Shou Hsieh ◽  
Tzy-Yen Chen ◽  
Hui-Ling Chiou
Keyword(s):  
Cell Apoptosis ◽  
Caspase 3 ◽  
Natural Food ◽  
Dependent Manner ◽  
Caspase Activation ◽  
Huh7 Cells ◽  
Dependent Cell ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
Autophagy Inhibition

Extensive research results support the application of herbal medicine or natural food as an augment during therapy for various cancers. However, the effect of dioscin on tumor cells autophagy has not been clearly clarified. In this study, the unique effects of dioscin on autophagy of hepatoma cells were investigated. Results found that dioscin induced caspase-3- and -9-dependent cell apoptosis in a dose-dependent manner. Moreover, inhibition of ERK1/2 phosphorylation significantly abolished the dioscin-induced apoptosis. In addition, dioscin triggered cell autophagy in early stages. With autophagy inhibitors to hinder the autophagy process, dioscin-induced cell apoptosis was significantly enhanced. An inhibition of caspase activation did not affect the dioscin-induced LC3-II protein expression. Based on the results, we believed that while apoptosis was blocked, dioscin-induced autophagy process also diminished in Huh7 cells. In conclusion, this study indicates that dioscin causes autophagy in Huh7 cells and suggests that dioscin has a cytoprotective effect.

scholarly journals PRIC295, a Nuclear Receptor Coactivator, Identified from PPAR-Interacting Cofactor Complex

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-16 ◽  
Author(s):  
Sean R. Pyper ◽  
Navin Viswakarma ◽  
Yuzhi Jia ◽  
Yi-Jun Zhu ◽  
Joseph D. Fondell ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Target Genes ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Receptor Coactivator ◽  
Evolutionarily Conserved

The peroxisome proliferator-activated receptor- (PPAR) plays a key role in lipid metabolism and energy combustion. Chronic activation of PPAR in rodents leads to the development of hepatocellular carcinomas. The ability of PPAR to induce expression of its target genes depends on Mediator, an evolutionarily conserved complex of cofactors and, in particular, the subunit 1 (Med1) of this complex. Here, we report the identification and characterization of PPAR-interacting cofactor (PRIC)-295 (PRIC295), a novel coactivator protein, and show that it interacts with the Med1 and Med24 subunits of the Mediator complex. PRIC295 contains 10 LXXLL signature motifs that facilitate nuclear receptor binding and interacts with PPAR and five other members of the nuclear receptor superfamily in a ligand-dependent manner. PRIC295 enhances the transactivation function of PPAR, PPAR, and ER. These data demonstrate that PRIC295 interacts with nuclear receptors such as PPAR and functions as a transcription coactivator underin vitroconditions and may play an important role in mediating the effectsin vivoas a member of the PRIC complex with Med1 and Med24.

scholarly journals Hydroxytyrosol Ameliorates Endothelial Function under Inflammatory Conditions by Preventing Mitochondrial Dysfunction

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Nadia Calabriso ◽  
Antonio Gnoni ◽  
Eleonora Stanca ◽  
Alessandro Cavallo ◽  
Fabrizio Damiano ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Mitochondrial Function ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflamed Endothelium

Mitochondria are fundamental organelles producing energy and reactive oxygen species (ROS); their impaired functions play a key role in endothelial dysfunction. Hydroxytyrosol (HT), a well-known olive oil antioxidant, exerts health benefits against vascular diseases by improving endothelial function. However, the HT role in mitochondrial oxidative stress in endothelial dysfunction is not clear yet. To investigate the HT effects on mitochondrial ROS production in the inflamed endothelium, we used an in vitro model of endothelial dysfunction represented by cultured endothelial cells, challenged with phorbol myristate acetate (PMA), an inflammatory, prooxidant, and proangiogenic agent. We found that the pretreatment of endothelial cells with HT (1–30 μmol/L) suppressed inflammatory angiogenesis, a crucial aspect of endothelial dysfunction. The HT inhibitory effect is related to reduced mitochondrial superoxide production and lipid peroxidation and to increased superoxide dismutase activity. HT, in a concentration-dependent manner, improved endothelial mitochondrial function by reverting the PMA-induced reduction of mitochondrial membrane potential, ATP synthesis, and ATP5β expression. In PMA-challenged endothelial cells, HT also promoted mitochondrial biogenesis through increased mitochondrial DNA content and expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, nuclear respiratory factor-1, and mitochondrial transcription factor A. These results highlight that HT blunts endothelial dysfunction and pathological angiogenesis by ameliorating mitochondrial function, thus suggesting HT as a potential mitochondria-targeting antioxidant in the inflamed endothelium.

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