Butyric Acid Induces Apoptosis in Inflamed Fibroblasts

2008 ◽  
Vol 87 (1) ◽  
pp. 51-55 ◽  
Author(s):  
T. Kurita-Ochiai ◽  
S. Seto ◽  
N. Suzuki ◽  
M. Yamamoto ◽  
K. Otsuka ◽  
...  
Keyword(s):  
Butyric Acid ◽  
Caspase 3 ◽  
Chromatin Condensation ◽  
Dependent Manner ◽  
Gingival Fibroblasts ◽  
T And B Cells ◽  
Healthy Humans ◽  
Extracellular Metabolite ◽  
Induced Apoptosis ◽  
Dose Dependent

Butyric acid, an extracellular metabolite from periodontopathic bacteria, induces apoptosis in murine and human T- and B-cells, whereas intact gingival fibroblasts isolated from healthy humans are resistant to butyric-acid-induced apoptosis. We examined the susceptibility of inflamed gingival fibroblasts isolated from adult persons with periodontitis to butyric-acid-induced apoptosis. Butyric acid significantly suppressed the viability of inflamed gingival fibroblasts and induced apoptosis in a dose-dependent manner. The incubation of inflamed gingival fibroblasts with butyric acid induced DNA fragmentation and apoptotic changes such as chromatin condensation, hypodiploid nuclei, and mitochondrial injury. Furthermore, butyric-acid-induced apoptosis in inflamed gingival fibroblasts was reduced by caspase-3/7, -6, -8, and -9 inhibitors. Thus, inflamed gingival fibroblasts from adult persons with periodontitis appear to be highly susceptible to mitochondria- and caspase-dependent apoptosis induced by butyric acid, compared with healthy gingival fibroblasts.

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.

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.

A Novel Mechanism of Nilotinib-Induced Apoptosis; Sphingolipids.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4246-4246
Author(s):  
Yusuf Baran ◽  
Emel Basak Gencer ◽  
Aylin Camgoz ◽  
Ferit Avcu ◽  
Ali Ugur Ural
Keyword(s):  
Cell Cycle ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
De Novo ◽  
Dependent Manner ◽  
Ceramide Synthase ◽  
Proliferation Assay ◽  
Rt Pcr ◽  
Induced Apoptosis ◽  
Dose Dependent

Abstract Abstract 4246 Chronic myeloid leukemia (CML) is a hematological malignancy resulting from the reciprocal translocation of chromosomes 9 and 22 that generates BCR/ABL oncogene. Nilotinib is a rationally designed, specific BCR/ABL tyrosine kinase inhibitor. Ceramide is a novel regulator of cell growth and proliferation, differentiation, senescence, cell cycle and also acts a strong apoptotic molecule while its conversion to antiapoptotic glucosyle ceramide (GC) and sphingosine-1-phosphate (S1P) by glucosyle ceramide synthase (GCS) and sphingosine kinase-1 (SK-1) enzymes result in more aggressive and resistant cancers. In this study, we studied the roles of ceramide metabolising genes in nilotinib induced apoptosis and possibility of increasing the sensitivity of BCR/ABL positive K562 and Meg-01 cells to nilotinib through targeting ceramide metabolism. The cytotoxicity analyses of nilotinib, C8:ceramide to induce de novo generation of ceramides, 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) to inhibit GCS and SK1 inhibitor were conducted by XTT cell proliferation assay. The changes in caspase-3 enzyme activity and mitochondrial membrane potential (MMP) were measured by caspase-3 colorimetric assay and JC-1 MMP detection kit, respectively. Expression analyses of ceramide synthase (LASS) genes, SK-1 and GCS genes were performed by RT-PCR. We have shown that nilotinib induces apoptosis and inhibits cell-cycle progression in K562 and Meg-01 cells in a dose dependent manner. We have shown significant synergistic apoptotic effects of nilotinib in combination with C8:ceramide or PDMP or SK-1 inhibitor by XTT cell proliferation assay in addition to the changes in caspase-3 enzyme activity and changes in mitochondrial membrane potential, as compared to any agent alone. These results revealed that increasing de novo generation of ceramides or inhibiting conversion of ceramides to antiapoptotic GC or S1P increased sensitivity of BCR/ABL CML cells to nilotinib. More importantly, RT-PCR results revealed that there were significant decreases in expression levels of SK1 in response to increasing concentrations of nilotinib. On the other hand increases in expression levels of LASS2, -4, -5, and -6 ceramide synthase genes were determined in a dose dependent manner as compared to untreated controls. It was shown for the first time by this study that targeting ceramide metabolism in addition to inhibition of BCR/ABL by nilotinib induces apoptosis synergistically in BCR/ABL positive K562 and Meg-01 CML cells. This study was supported by The Scientific and Technological Council of Turkey Disclosures: No relevant conflicts of interest to declare.

UV-Induced Apoptosis in Resistant HeLa Cells

2000 ◽  
Vol 20 (2) ◽  
pp. 99-108 ◽  
Author(s):  
P. Kamarajan ◽  
Chuck C.-K. Chao
Keyword(s):  
Hela Cells ◽  
Caspase 3 ◽  
Chromatin Condensation ◽  
Time Dependent ◽  
Consistent Difference ◽  
Dependent Manner ◽  
Downstream Target ◽  
Signaling Complex ◽  
Induced Apoptosis ◽  
Resistant Cells

Recently, apoptosis (genetically programmed cell death) induced by UV hasbeen documented in some cell culture models. However, the significance ofapoptosis in UV-induced cytotoxicity and resistance is uncertain. In thisstudy, we investigated the induction of apoptosis in HeLa cells and itsrole in acquired UV-resistance. The membrane receptor Fas was induced toassembly, and its immediate downstream target, caspase-8, was induced byUV in a dose- and time-dependent manner. Caspase-10, another possiblecandidate for forming the death-inducing signaling complex with Fas, wasalso activated in a dose- and time-dependent manner. There was significantactivation of caspase 9, 3 and 2 by UV. The apoptotic pathways appeared tobe normal in acquired UV-resistant HeLa cells. In addition, there was a UVdose-dependent induction of chromatin condensation in both parental andUV-resistant cells. However, resistant cells displayed significant reductionin chromatin condensation at lower doses. Inhibition of caspase-3 activation byspecific inhibitor significantly reduced the chromatin condensation in bothcell types, and unexpectedly, the difference between the two cell lines wascompletely eradicated, suggesting that the caspase-3 pathway plays asignificant role in reducing apoptosis in resistant cells. The resultsindicate that UV induces apoptosis by direct activation of apoptoticproteins in HeLa and resistant cells. Although resistant cells displayedpartial inhibition of UV-induced apoptosis through the caspase-3 pathway,there was no consistent difference in the activation of this and relatedcaspase-9 caspases compared to parental HeLa cells.

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.

scholarly journals Escherichia coli Shiga-Like Toxins Induce Apoptosis and Cleavage of Poly(ADP-Ribose) Polymerase via In Vitro Activation of Caspases

2002 ◽  
Vol 70 (8) ◽  
pp. 4669-4677 ◽  
Author(s):  
Joyce C. Y. Ching ◽  
Nicola L. Jones ◽  
Peter J. M. Ceponis ◽  
Mohamed A. Karmali ◽  
Philip M. Sherman
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Intracellular Signaling ◽  
Chromatin Condensation ◽  
Specific Inhibitor ◽  
Caspase 8 ◽  
High Dose ◽  
Dependent Manner ◽  
Induced Apoptosis ◽  
Dose Dependent

ABSTRACT Shiga-like toxin-producing Escherichia coli causes hemorrhagic colitis and hemolytic-uremic syndrome in association with the production of Shiga-like toxins, which induce cell death via either necrosis or apoptosis. However, the abilities of different Shiga-like toxins to trigger apoptosis and the sequence of intracellular signaling events mediating the death of epithelial cells have not been completely defined. Fluorescent dye staining with acridine orange and ethidium bromide showed that Shiga-like toxin 1 (Stx1) induced apoptosis of HEp-2 cells in a dose- and time-dependent manner. Stx2 also induced apoptosis in a dose-dependent manner. Apoptosis induced by Stx1 (200 ng/ml) and apoptosis induced by Stx2 (200 ng/ml) were maximal following incubation with cells for 24 h (94.3% ± 1.8% and 81.7% ± 5.2% of the cells, respectively). Toxin-treated cells showed characteristic features of apoptosis, including membrane blebbing, DNA fragmentation, chromatin condensation, cell shrinkage, and the formation of apoptotic bodies, as assessed by transmission electron microscopy. Stx2c induced apoptosis weakly even at a high dose (1,000 ng/ml for 24 h; 26.7% ± 1.3% of the cells), whereas Stx2e did not induce apoptosis of HEp-2 cells. Thin-layer chromatography confirmed that HEp-2 cells express the Stx1-Stx2-Stx2c receptor, globotriaosylceramide (Gb3), but not the Stx2e receptor, globotetraosylceramide (Gb4). Western blot analysis of poly(ADP-ribose) polymerase (PARP), a DNA repair enzyme, demonstrated that incubation with Stx1 and Stx2 induced cleavage, whereas incubation with Stx2e did not result in cleavage of PARP. A pan-caspase inhibitor (Z-VAD-FMK) and a caspase-8-specific inhibitor (Z-IETD-FMK) eliminated, in a dose-dependent fashion, the cleavage of PARP induced by Shiga-like toxins. Caspase-8 activation was confirmed by detection of cleavage of this enzyme by immunoblotting. Cleavage of caspase-9 and the proapoptotic member of the Bcl-2 family BID was also induced by Stx1, as determined by immunoblot analyses. We conclude that different Shiga-like toxins induce different degrees of apoptosis that correlates with toxin binding to the glycolipid receptor Gb3 and that caspases play an integral role in the signal transduction cascade leading to toxin-mediated programmed cell death.

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 Hop-derived Xanthohumol Induces HL-60 Leukemia Cells Death

2020 ◽  
pp. 61-72
Author(s):  
M. Pacurari ◽  
H. Brown ◽  
A. Rieland
Keyword(s):  
Cell Viability ◽  
Cell Cycle Progression ◽  
Caspase 3 ◽  
Morphological Changes ◽  
Chromatin Condensation ◽  
Dependent Manner ◽  
Cycle Progression ◽  
Humulus Lupulus L ◽  
Additional Chemotherapy ◽  
Dose Dependent

Background: Acute promyelocytic leukemia (APL) affects both kids and adults, however it is more prevalent in younger population. Although APL has a favorable prognostic, patients that relapse often do not respond positively to additional chemotherapy. Therefore, there is a need to further identify ways to overcome these challenges.  Hypothesis: In this study, we examined antileukemic effects of xanthohumol (XN), a prenylated flavonoid derived from hops (Humulus lupulus L), on human promyelocytic HL-60 cells.  Materials and Methods: HL-60 cells were exposed to different concentrations of XN (μM) for 24 h. Cell viability, cell morphology, chromatin condensation, cPARP-1 level, and caspase-3 activation, and the expression of p21WAF1/Cip1 were analyzed. Results: XN reduced HL-60 cell viability in a dose-dependent manner. XN induced a dose-dependent morphological changes including cell shrinkage and blebbing, and significantly increased the number of cells with condensed chromatin. XN significantly increased the level of cPARP-1, active caspase-3, and the expression of p21WAF/CIP mRNA. Conclusion: These data indicate that XN induces HL-60 cell death by regulating cell cycle progression and apoptosis. This study suggests that XN may have antileukemic preventive effects.

Up-Regulation of Death Receptor 5 and Bax Translocation Is Necessary To Induce Apoptosis by Sanguinarine in Primary Effusion Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4615-4615 ◽  
Author(s):  
Azhar R. Hussain ◽  
Naif A. Al-Jomah ◽  
Abdul K. Siraj ◽  
Manugaran S. Pulicat ◽  
Khaled A. Al-Hussein ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cytochrome C ◽  
Cell Lines ◽  
Caspase 3 ◽  
Primary Effusion Lymphoma ◽  
Death Receptor ◽  
Dependent Manner ◽  
Death Receptor 5 ◽  
Induced Apoptosis ◽  
Dose Dependent

Abstract Primary effusion lymphoma (PEL) is an aggressive and fatal type of cancer. PEL cells produce a variety of autocrine cytokines and growth factors, which provides cyto-protection against conventional chemotherapeutic agents. In efforts to identify novel approaches to block the proliferation of PEL cells, we found that Sanguinarine, a natural compound isolated from the root plant Sanguinaria canadendid, that is being used as an anti-microbial agent, inhibited cell proliferation and induced apoptosis in a dose dependent manner in several PEL cell lines through a bax-dependent signaling pathway. Five PEL cell lines used in this study were treated with various doses of Sanguinarine ranging between 0.5–4μM inhibited cell proliferation in all the cell lines in a dose dependent manner (BC1 40–97%, BC3 46–93%, BCBL1 11–94%, BCP1 20–97% and HBL6 7–95%). Treatment with varying doses of Sanguinarine also induced apoptosis in all cell lines as determined by cell cycle analysis, annexinV/PI dual staining, TUNEL assay and DNA laddering. Sanguinarine treatment resulted in up-regulation of death receptor 5 (DR5) expression, activation of caspase-8 and Bid leading to Bax conformational changes and translocation to the mitochondrial causing loss of mitochondrial membrane potential as measured by JC1 staining and release of cytochrome c to the cytosole. Sanguinarine induced release of cytochrome c resulted in activation of caspase-3, followed by polyadenosin-5′-diphosphate-ribose polymerase (PARP) cleavage leading to inhibition of proliferation and induction of caspase-dependent apoptosis. Furthermore, pre-treatment of PEL cells with z-VAD-fmk, a universal inhibitor of caspases, abrogated caspase-3 and PARP activation and prevented cell death induced by Sanguinarine. Inhibitor of apoptosis proteins (IAPs), play an important role in protecting cells against apoptosis through their direct action on caspases-9 and -3. Treatment of PEL cells with Sanguinarine down-regulated the expression of IAPs; XIAP, cIAP1 and cIAP2. Taken altogether, our findings suggest that Sanguinarine induces apoptosis via up-regulation of DR5, activation of Bax in a caspase-dependent pathway and down-regulation of IAPs. These results provide the molecular basis and preliminary data for new treatment strategies that may incorporate Sanguinarine in regimens for primary effusion lymphoma treatment.

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.

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