Micronucleus formation during chromatin condensation and under apoptotic conditions
AbstractIn early S phase the newly replicated DNA is folded back to increasingly compact structures. The process of chromatin condensation inside the nucleus starts with the formation of a micronucleus observed in five established cell lines (K562, CHO, Indian muntjac, murine preB and SCC). Supercoiling of chromatin generates a polarized end-plate region extruded from the nucleus. The extruded chromatin is turned around itself forming the head portion (micronucleus) visible by fluorescence microscopy until the middle of S phase when chromatin structures are succeeded by distinguishable early forms of chromosomes. The gener...
Source: Apoptosis - October 25, 2016 Category: Molecular Biology Source Type: research

Insights on the involvement of ( –)-epigallocatechin gallate in ER stress-mediated apoptosis in age-related macular degeneration
AbstractEndoplasmic reticulum (ER) stress-mediated apoptosis is a well-known factor in the pathogenesis of age-related macular degeneration (AMD). ER stress leads to accumulation of misfolded proteins, which in turn activates unfolded protein response (UPR) of the cell for its survival. The prolonged UPR of ER stress promotes cell death; however, the transition between adaptation and ER stress-induced apoptosis has not been clearly understood. Hence, the present study investigates the regulatory effect of ( –)-epigallocatechin gallate (EGCG) on ER stress-induced by hydrogen peroxide (H2O2) and disturbance of calcium ...
Source: Apoptosis - October 24, 2016 Category: Molecular Biology Source Type: research

Gadolinium induced effects on mammalian cell motility, adherence and chromatin structure
AbstractThe toxicity of gadolinium is reduced by chelating agents that render this heavy metal into contrast complexes used for medical magnetic resonance imaging. However, the dissociation of gadolinium chelates is known to generate Gd3+ ions, the cellular toxicity of which has not been tested in details. The cytotoxic effects of Gd(III) ions were evaluated by monitoring the proliferation, measuring the cellular motility and following chromatin changes in various cell lines upon Gd3+ treatment. Measurements applied long-term scanning microscopy and a perfusion platform that replaced the medium with test solutions, bypasse...
Source: Apoptosis - October 22, 2016 Category: Molecular Biology Source Type: research

Coenzyme Q10 protects renal proximal tubule cells against nicotine-induced apoptosis through induction of p66 shc -dependent antioxidant responses
This study explored the anti-oxidant /anti-apoptotic effect of Coenzyme Q10 on nicotine-induced oxidative stress and its impact on p66shc in cultured rat renal proximal tubule cells (NRK52E). We studied the anti-oxidant effect of 10 µM Coenzyme Q10 using various mutants of the p66shc gene and also determined the induction of selected anti-oxidant entities (antioxidant response element, promoter of the manganese superoxide dismutase gene) in reporter luciferase assay during oxidative stress induced by 200 µM nicotine. Our studies revealed that Coenzyme Q10 strongly inhibits nicotine-mediated production...
Source: Apoptosis - October 22, 2016 Category: Molecular Biology Source Type: research

2-aryl benzimidazole conjugate induced apoptosis in human breast cancer MCF-7 cells through caspase independent pathway
AbstractApoptosis is a representative form of programmed cell death, which has been assumed to be critical for cancer prevention. Thus, any agent that can induce apoptosis may be useful for cancer treatment and apoptosis induction is arguably the most potent defense against cancer promotion. In our previous studies, 2-aryl benzimidazole conjugates were synthesized and evaluated for their antiproliferative activity and one of the new molecule (2f) was considered as a potential lead. This lead molecule showed significant antiproliferative activity against human breast cancer cell line, MCF-7. The results of the present study...
Source: Apoptosis - October 21, 2016 Category: Molecular Biology Source Type: research

Sensitizing effect of juglone is mediated by down regulation of Notch1 signaling pathway in trastuzumab-resistant SKBR3 cells
In this study, we were aimed to investigate whether the cross talk between pin1 and Notch1 has a role in this event. Our results indicated that the expression level of Pin1 in resistant SKBR3 cells increased by about twofold relative to sensitive SKBR3 cells. Besides, Pin1 inhibition via juglone reduced the extent of proliferation, colony formation and migration capacity of resistant SKBR3 cells. In addition, despite a feed forward loop between Notch1 and Pin1 in sensitive SKBR3 cells, inhibition of Notch1 cleavage in resistant SKBR3 cells did not affect pin1 level whereas pin1 inhibition by juglone reduced the level of He...
Source: Apoptosis - October 21, 2016 Category: Molecular Biology Source Type: research

MG132 plus apoptosis antigen-1 (APO-1) antibody cooperate to restore p53 activity inducing autophagy and p53-dependent apoptosis in HPV16 E6-expressing keratinocytes
AbstractThe E6 oncoprotein can interfere with the ability of infected cells to undergo programmed cell death through the proteolytic degradation of proapoptotic proteins such as p53, employing the proteasome pathway. Therefore, inactivation of the proteasome through MG132 should restore the activity of several proapoptotic proteins. We investigated whether in HPV16 E6-expressing keratinocytes (KE6 cells), the restoration of p53 levels mediated by MG132 and/or activation of the CD95 pathway through apoptosis antigen-1 (APO-1) antibody are responsible for the induction of apoptosis. We found that KE6 cells underwent apoptosi...
Source: Apoptosis - October 20, 2016 Category: Molecular Biology Source Type: research

A3K2A3-induced apoptotic cell death of Leishmania amazonensis occurs through caspase- and ATP-dependent mitochondrial dysfunction
AbstractLeishmaniasis is a neglected tropical disease that affects millions of people worldwide. Current therapies mainly rely on antimonial drugs that are inadequate because of their high toxicity and increased drug resistance. An urgent need exists to discover new, more effective, more affordable, and more target-specific drugs. Pathways that are associated with apoptosis-like cell death have been identified in unicellular eukaryotes, including protozoan parasites. In the present study, we studied the mechanism of cell death that is induced by A3K2A3 againstL. amazonensis. A3K2A3 is a dibenzylideneacetone that has an acy...
Source: Apoptosis - October 19, 2016 Category: Molecular Biology Source Type: research

Amsacrine-induced apoptosis of human leukemia U937 cells is mediated by the inhibition of AKT- and ERK-induced stabilization of MCL1
AbstractPrevious studies have attributed the anticancer activity of amsacrine to its inhibitory effect on topoisomerase II. However, 9-aminoacridine derivatives, which have the same structural scaffold as amsacrine, induce cancer cell apoptosis by altering the expression of BCL2 family proteins. Therefore, in the present study, we assessed whether BCL2 family proteins mediated the cytotoxic effects of amsacrine on human leukemia U937 cells. Amsacrine-induced apoptosis of U937 cells was characterized by caspase-9 and caspase-3 activation, increased intracellular Ca2+ concentration, mitochondrial depolarization, and MCL1 dow...
Source: Apoptosis - October 19, 2016 Category: Molecular Biology Source Type: research

Adiponectin exerts cardioprotection against ischemia/reperfusion injury partially via calreticulin mediated anti-apoptotic and anti-oxidative actions
AbstractThe underlying mechanisms of cardioprotection of adiponectin (APN) against ischemia/reperfusion (I/R) injury remain largely unknown. The present study aimed to investigate whether calreticulin (CRT) mediated APN ’s cardioprotection against I/R injury. We inhibited mice cardiac CRT expression via intra-myocardial injection of CRT SiRNA, performed transient LAD ligation, measured the cardiac function, apoptosis and oxidative stress to identify CRT’s effects on cardioprotective actions of APN against I/R i njury in vivo. LDH release and expression of CRT were measured in neonatal cardiomyocytes (NCM) subje...
Source: Apoptosis - October 18, 2016 Category: Molecular Biology Source Type: research

Photo-modulation of programmed cell death in rice leaves triggered by salinity
AbstractIn this paper we provide evidence for involvement of chloroplast as alternate organelle for initiating PCD in plants under light and abiotic stress. In animals, mitochondria are the major source of reactive oxygen species (ROS) and key executioner of programmed cell death (PCD). In plants, however, the primary site of generation of ROS is chloroplast and yet its involvement in PCD has not been worked out in details. We found by Evans blue staining that salt (150  mM NaCl)-treated protoplasts obtained from green seedlings had higher rate of cell death than protoplasts obtained from etiolated seedlings. This ind...
Source: Apoptosis - October 17, 2016 Category: Molecular Biology Source Type: research

The cardioprotective effect of dihydromyricetin prevents ischemia –reperfusion-induced apoptosis in vivo and in vitro via the PI3K/Akt and HIF-1α signaling pathways
AbstractReperfusion therapy is widely used to treat acute myocardial infarction (AMI). However, further injury to the heart induced by rapidly initiating reperfusion is often encountered in clinical practice. A lack of pharmacological strategies in clinics limits the prognosis of patients with myocardial ischemia-reperfusion injury (MIRI). Dihydromyricetin (DMY) is one of the most abundant components in vine tea, commonly known as the tender stems and leaves ofAmpelopsis grossedentata. The aim of this study was to evaluate the cardioprotection of DMY against myocardial ischemia-reperfusion (I/R) injury and to further inves...
Source: Apoptosis - October 13, 2016 Category: Molecular Biology Source Type: research

The marine cytotoxin portimine is a potent and selective inducer of apoptosis
In this study we show that portimine kills human Jurkat T-lymphoma cells and mouse embryonic fibroblasts (MEFs), with LC50 values of 6 and 2.5  nM respectively. Treated cells displayed rapid caspase activation and phosphatidylserine exposure, indicative of apoptotic cell death. Jurkat cells overexpressing the anti-apoptotic protein Bcl-2 or Bax/Bak knockout MEFs were completely protected from portimine. This protection was apparent even a t high concentrations of portimine, with no evidence of necrotic cell death, indicating that portimine is a selective chemical inducer of apoptosis. Treatment of the Bcl-2-overexpres...
Source: Apoptosis - October 13, 2016 Category: Molecular Biology Source Type: research

Targeted knockdown of DJ-1 induces multiple myeloma cell death via KLF6 upregulation
AbstractMultiple myeloma (MM) is an incurable plasma B cell malignancy. Despite recent advancements in anti-MM therapies, development of drug resistance remains a major clinical hurdle. DJ-1, a Parkinson ’s disease-associated protein, is upregulated in many cancers and its knockdown suppresses tumor growth and overcomes chemoresistance. However, the role of DJ-1 in MM remains unknown. Using gene expression databases we found increased DJ-1 expression in MM patient cells, which correlated with shor ter overall survival and poor prognosis in MM patients. Targeted DJ-1 knockdown using siRNAs induced necroptosis in myelo...
Source: Apoptosis - October 12, 2016 Category: Molecular Biology Source Type: research

GART mediates the renewal of intestinal epithelial barrier via p38/p53/PUMA cascade in colitis
AbstractGlycinamide ribonucleotide formyltransferase (GART) has been established as a pivotal enzyme in de novo purine synthesis, and mediates cellular apoptosis in many diseases. We aimed to investigate the role of GART in the pathogenesis of Crohn ’s disease (CD). In our study, we demonstrated for the first time that GART expression is up-regulated in patients with active CD and in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced acute colitis model. Moreover, the inhibition of GART induced cellular apoptosis and suppressed the migration of IECs through the activation of the MEKK3-MKK3-p38 mitogen-activated prote...
Source: Apoptosis - October 7, 2016 Category: Molecular Biology Source Type: research

Identification of cytotoxic mediators and their putative role in the signaling pathways during docosahexaenoic acid (DHA)-induced apoptosis of cancer cells
AbstractDocosahexaenoic acid (DHA), an important w-3 fatty acid exhibits differential behavior in cancer cells of neural origin when compared to that in normal healthy astrocytes. Treatment of C6 glioma and SH-SY5Y cell lines and primary astrocytes, representing the neoplastic cells and normal healthy cells respectively, with 100  µM DHA for 24 h showed significant loss of cell viability in the both the cancer cells as determined by MTT assay, whereas the primary astrocytes cultures were unaffected. Such loss of cell viability was due to apoptosis as confirmed by TUNEL staining and caspase-3 activation in c...
Source: Apoptosis - October 4, 2016 Category: Molecular Biology Source Type: research

Dynamic quantitative proteomics characterization of TNF- α-induced necroptosis
AbstractEmerging evidence suggested that necroptosis has essential functions in many human inflammatory diseases, but the molecular mechanisms of necroptosis remain unclear. Here, we employed SILAC quantitatively dynamic proteomics to compare the protein changes during TNF- α-induced necroptosis at different time points in murine fibrosarcoma L929 cells with caspase-8 deficiency, and then performed the systematical analysis on the signaling networks involved in the progress using bioinformatics methods. Our results showed that a total of 329, 421 and 378 differentiall y expressed proteins were detected at three stage...
Source: Apoptosis - October 4, 2016 Category: Molecular Biology Source Type: research

Peripheral blood mononuclear cell secretome for tissue repair
AbstractFor almost two decades, cell-based therapies have been tested in modern regenerative medicine to either replace or regenerate human cells, tissues, or organs and restore normal function. Secreted paracrine factors are increasingly accepted to exert beneficial biological effects that promote tissue regeneration. These factors are called the cell secretome and include a variety of proteins, lipids, microRNAs, and extracellular vesicles, such as exosomes and microparticles. The stem cell secretome has most commonly been investigated in pre-clinical settings. However, a growing body of evidence indicates that other cel...
Source: Apoptosis - October 1, 2016 Category: Molecular Biology Source Type: research

Synergistic protective effect of paeoniflorin and β-ecdysterone against rotenone-induced neurotoxicity in PC12 cells
This study evaluates the hypothesis that paeoniflorin (PF) and β-ecdysterone (β-Ecd) synergize to protect PC12 cells against toxicity induced by PD-related neurotoxin ro tenone. The combination of PF and β-Ecd, hereafter referred to as the PF/β-Ecd, at suboptimal concentrations increased the viability of rotenone-exposed PC12 cells in a synergistic manner. PF and β-Ecd cooperate to attenuate the rotenone-induced apoptosis by decrease in Bax expression, caspase-9 activity, and caspase-3 activity. PF or PF/β-Ecd, but not β-Ecd, inhibited rotenone-triggered protein kinase C-δkinase C-&...
Source: Apoptosis - September 29, 2016 Category: Molecular Biology Source Type: research

Oxymatrine synergistically enhances antitumor activity of oxaliplatin in colon carcinoma through PI3K/AKT/mTOR pathway
AbstractOxymatrine (OMT), one of the main active components of extracts from the dry roots of Sophora flavescens, has been reported to possess many pharmacological properties including cancer-preventive and anti-cancer effects. The aim of the present study is to explore the efficiency of combination therapy with OMT and oxaliplatin (OXA) and identify the in vitro and in vivo cytotoxicity on colon cancer lines (HT29 and SW480) and mice model. Cells were treated with OMT and/or OXA and subjected to cell viability, colony formation, apoptosis, cell cycle, western blotting, xenograft tumorigenicity assay and immunohistochemist...
Source: Apoptosis - September 26, 2016 Category: Molecular Biology Source Type: research

Mitochondrial dynamics during cell cycling
AbstractMitochondria are the cell ’s power plant that must be in a proper functional state in order to produce the energy necessary for basic cellular functions, such as proliferation. Mitochondria are ‘dynamic’ in that they are constantly undergoing fission and fusion to remain in a functional state throughout the cell cycle, as well as during other vital processes such as energy supply, cellular respiration and programmed cell death. The mitochondrial fission/fusion machinery is involved in generating young mitochondria, while eliminating old, damaged and non-repairable ones. As a result, the organelles...
Source: Apoptosis - September 23, 2016 Category: Molecular Biology Source Type: research

The ROS derived mitochondrial respirstion not from NADPH oxidase plays key role in Celastrol against angiotensin II-mediated HepG2 cell proliferation
In this study, we studied the effect of celastrol on AngII-induced HepG2 cell proliferation and evaluated its underlying mechanism. The results revealed that AngII was able to significantly promote HepG2 cell proliferation via up-regulating AngII type 1 (AT1) receptor expression, improving mitochondrial respiratory function, enhancing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, increasing the levels of reactive oxygen species (ROS) and pro-inflammatory cytokines. The excess ROS from mitochondrial dysfunction is able to cause the apoptosis of tumor cells via activating caspase3 signal pathway. In a...
Source: Apoptosis - September 22, 2016 Category: Molecular Biology Source Type: research

Endoplasmic reticulum (ER) stress triggers Hax1-dependent mitochondrial apoptotic events in cardiac cells
AbstractCardiomyocyte apoptosis is a major process in pathogenesis of a number of heart diseases, including ischemic heart diseases and cardiac failure. Ensuring survival of cardiac cells by blocking apoptotic events is an important strategy to improve cardiac function. Although the role of ER disruption in inducing apoptosis has been demonstrated, we do not yet fully understand how it influences the mitochondrial apoptotic machinery in cardiac cell models. Recent investigations have provided evidences that the prosurvival protein HCLS1-associated protein X-1 (Hax1) protein is intimately associated with the pathogenesis of...
Source: Apoptosis - September 21, 2016 Category: Molecular Biology Source Type: research

Mycophenolic acid potentiates HER2-overexpressing SKBR3 breast cancer cell line to induce apoptosis: involvement of AKT/FOXO1 and JAK2/STAT3 pathways
AbstractTrastuzumab has been successfully used as a first-line therapy specific for HER2-overexressing breast cancer patients. However, despite the effectiveness of trastuzumab, the occurrence of inherent and acquired resistance remains as the main challenge of the therapy. Thus, this has motivated efforts toward finding new therapeutic strategies including combining trastuzumab with other drugs to enhance its therapeutic efficacy. In that line, we investigated the capability of mycophenolic acid (MPA), an inhibitor of de novo guanine nucleotide synthesis with potential anti-cancer activity, on improving the response to tr...
Source: Apoptosis - September 20, 2016 Category: Molecular Biology Source Type: research

Pim kinase isoforms: devils defending cancer cells from therapeutic and immune attacks
AbstractPim kinases are being implicated in oncogenic process in various human cancers. Pim kinases primarily deal with three broad categories of functions such as tumorigenesis, protecting cells from apoptotic signals and evading immune attacks. Here in this review, we discuss the regulation of Pim kinases and their expression, and how these kinases defend cancer cells from therapeutic and immune attacks with special emphasis on how Pim kinases maintain their own expression during apoptosis and cellular transformation, defend mitochondria during apoptosis, defend cancer cells from immune attack, defend cancer cells from t...
Source: Apoptosis - September 20, 2016 Category: Molecular Biology Source Type: research

Gefitinib enhances human colon cancer cells to TRAIL-induced apoptosis of via autophagy- and JNK-mediated death receptors upregulation
AbstractTumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent cancer cell-specific apoptosis-inducing cytokine with little toxicity to most normal cells. Here, we report that gefitinib and TRAIL in combination produce a potent synergistic effect on TRAIL-sensitive human colon cancer HCT116 cells and an additive effect on TRAIL-resistant HT-29 cells. Interestingly, gefitinib increases the expression of cell surface receptors DR4 and DR5, possibly explaining the synergistic effect. Knockdown of DR4 and DR5 by siRNA significantly decreases gefitinib- and TRAIL-mediated cell apoptosis, supporting th...
Source: Apoptosis - September 15, 2016 Category: Molecular Biology Source Type: research

Silver nanoparticles induce irremediable endoplasmic reticulum stress leading to unfolded protein response dependent apoptosis in breast cancer cells
AbstractNowadays, silver nanoparticles (AgNP) are widely used in the medical field mainly for their antibacterial properties. Although some studies report a cytotoxic activity of the particles, the mechanisms involved in AgNP-induced cell death remain to be determined. Herein, we report that AgNP of 2 (AgNP2) and 15  nm (AgNP15) induce apoptosis in human MCF-7 and T-47D breast cancer cells. Treatment with AgNP2 and AgNP15 led to accumulation and aggregation of misfolded proteins causing anendoplasmic reticulum (ER) stress and activating the unfolded protein response (UPR). The three main ER sensors, PERK, IRE-1 &alpha...
Source: Apoptosis - September 1, 2016 Category: Molecular Biology Source Type: research

The influence of exposure to immunosuppressive treatment during pregnancy on renal function and rate of apoptosis in native kidneys of female Wistar rats
AbstractPregnancy puts a significant additional strain on kidneys. The aim of our study was to investigate the impact of immunosuppressive drugs on changes in native kidneys in female Wistar rats after exposure during pregnancy. The study was conducted on 32 dams, subjected to immunosuppressive regimens commonly used in the therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; cyclosporine A, everolimus and prednisone). The animals received drugs for 2  weeks before pregnancy and during 3 weeks of pregnancy. In all tr...
Source: Apoptosis - September 1, 2016 Category: Molecular Biology Source Type: research

Alpha 5/6 helix domains together with N-terminus determine the apoptotic potency of the Bcl-2 family proteins
In this study, we generated a series of deletion mutants and substitution chimera, and used a combination of molecular biology, bio-informatics and living cell imaging techniques to answer these questions. Our major findings are: (1) All of the Bcl-2 family proteins appear to possess an intrinsic pro-apoptotic property. (2) The N-termini of these proteins play an active role in suppressing their pro-apoptotic function. (3) The apoptotic potency is positively correlated with membrane affinity of the alpha 5/6 helix domains. (4) Charge distribution flanking the alpha 5/6 helices is also important for the apoptotic potency. T...
Source: Apoptosis - August 23, 2016 Category: Molecular Biology Source Type: research

Targeting Nrf2 with wogonin overcomes cisplatin resistance in head and neck cancer
AbstractA principal limitation to the clinical use of cisplatin is the high incidence of chemoresistance to this drug. Combination treatments with other drugs may help to circumvent this problem. Wogonin, one of the major natural flavonoids, is known to reverse multidrug resistance in several types of cancers. We investigated the ability of wogonin to overcome cisplatin resistance in head and neck cancer (HNC) cells and further clarified its molecular mechanisms of action. Two cisplatin-resistant HNC cell lines (AMC-HN4R and -HN9R) and their parental and other human HNC cell lines were used. The effects of wogonin, either ...
Source: Apoptosis - August 20, 2016 Category: Molecular Biology Source Type: research

The sesquiterpene ( −)-α-bisabolol is active against the causative agents of Old World cutaneous leishmaniasis through the induction of mitochondrial-dependent apoptosis
AbstractCutaneous leishmaniasis treatment remains challenging due to the absence of a satisfactory treatment. The screening of natural compounds is a valuable strategy in the search of new drugs against leishmaniasis. The sesquiterpene ( −)-α-bisabolol is effective in vivo against visceral leishmaniasis due toLeishmania infantum, but its mechanism of action remains elusive. The aim of this study is to validate this promising compound against the causative species of Old World cutaneous leishmaniasis and to get an insight into its antileishmanial mode of action. The compound was evaluated onL. tropica promastigo...
Source: Apoptosis - August 18, 2016 Category: Molecular Biology Source Type: research

Pioglitazone inhibits advanced glycation end product-induced matrix metalloproteinases and apoptosis by suppressing the activation of MAPK and NF- κB
This study aims to evaluate the effect of pioglitazone on AGEs-induced chondrocyte apoptosis and degeneration and their underlying mechanism. The in vitro study shows that AGEs induce cleavage of caspase-3 and PARP, up-regulate MMP-13 express ion, enhance chondrocyte apoptosis and down-regulate PPARγ expression in human primary chondrocytes, which is reversed by pioglitazone. Furthermore, AGEs activate phosphorylation of Erk, JNK, and p38, and pioglitazone reverses AGEs-induced phosphorylation of Erk and p38. AGEs-induced degradation of IκBα and translocation of nuclear NF-κB p65 is reversed by piog...
Source: Apoptosis - August 11, 2016 Category: Molecular Biology Source Type: research

Novel SAHA analogues inhibit HDACs, induce apoptosis and modulate the expression of microRNAs in hepatocellular carcinoma
AbstractIn eukaryotes, transcriptional regulation occurs via chromatin remodeling, mainly through post translational modifications of histones that package DNA into structural units. Histone deacetylases (HDACs) are enzymes that play important role in various biological processes by repressing gene expression. Suberoylanilide hydroxamic acid (SAHA) is a known HDAC inhibitor that showed significant anti cancer activity by relieving gene silencing against hematologic and solid tumors. We have designed and synthesized a series of SAHA analogs C1 –C4 and performed biological studies to elucidate its anti-cancer effects. ...
Source: Apoptosis - August 8, 2016 Category: Molecular Biology Source Type: research

Amelotin gene expression is temporarily being upregulated at the initiation of apoptosis induced by TGF β1 in mouse gingival epithelial cells
AbstractAmelotin (AMTN) is expressed and secreted by ameloblasts in the maturation stage of amelogenesis and persist with low levels in the junctional epithelium (JE) of erupted teeth. The purpose of this study is to investigate the transcriptional regulation of the AMTN gene by transforming growth factor beta1 (TGF β1) in gingival epithelial (GE1) cells in the apoptosis phase. Apoptosis was evaluated by the fragmentation of chromosomal DNA and TUNEL staining. A real-time PCR was carried out to examine the AMTN mRNA levels induced by TGFβ1 and Smad3 overexpression. Transient transfection analyses were complet ed ...
Source: Apoptosis - August 8, 2016 Category: Molecular Biology Source Type: research

Endocannabinoids participate in placental apoptosis induced by hypoxia inducible factor-1
In this report, we evaluated the participation of ECs in placental apoptosis induced by cobalt chloride (CoCl2), a hypoxia mimicking agent that stabilizes the expression of hypoxia inducible factor-1 alpha (HIF-1 α). We found that HIF-1α stabilization decreased FAAH mRNA and protein levels, suggesting an increase in ECs tone. Additionally, CoCl2 incubation and Met-AEA treatment reduced cell viability and increased TUNEL-positive staining in syncytiotrophoblast layer. Immunohistochemical analysis demonstrated Bax and Bcl-2 protein expression in the cytoplasm of syncytiotrophoblast. Finally, HIF-1 α stabili...
Source: Apoptosis - August 3, 2016 Category: Molecular Biology Source Type: research

Vitamin E synthetic derivate —TPGS—selectively induces apoptosis in jurkat t cells via oxidative stress signaling pathways: implications for acute lymphoblastic leukemia
In conclusion, TPGS selectively induces apoptosis in Jurkat cells through two independent but complementary H2O2-mediated signaling pathways. Our findings support the use of TPGS as a potential treatment for ALL. (Source: Apoptosis)
Source: Apoptosis - August 2, 2016 Category: Molecular Biology Source Type: research

Calcitriol –copper interaction leads to non enzymatic, reactive oxygen species mediated DNA breakage and modulation of cellular redox scavengers in hepatocellular carcinoma
AbstractCalcitriol is the metabolically active form of Vitamin D and is known to kill cancer cells. Using the rat model of DEN induced hepatocellular carcinoma we show that there is a marked increase in cellular levels of copper in hepatocellular carcinoma and that calcitriol –copper interaction leads to reactive oxygen species mediated DNA breakage selectively in hepatocellular carcinoma cells. In vivo studies show that calcitriol selectively induces severe fluctuations in cellular enzymatic and non enzymatic scavengers of reactive oxygen species in the malignant tiss ue. Lipid peroxidation, a well established marke...
Source: Apoptosis - August 2, 2016 Category: Molecular Biology Source Type: research

Inhibition of autophagy by chloroquine induces apoptosis in primary effusion lymphoma in vitro and in vivo through induction of endoplasmic reticulum stress
In this study, we identified the role of CQ-induced cancer cell death using Primary Effusion Lymphoma (PEL) cells. We found that a CQ treatment induced caspase-dependent apoptosis in vitro. CQ also suppressed PEL cell growth in a PEL xenograft mouse model. We showed that CQ activated endoplasmic reticulum (ER) stress signal pathways and induced CHOP, which is an inducer of apoptosis. CQ-induced cell death was significantly decreased by salbrinal, an ER stress inhibitor, indicating that CQ-induced apoptosis in PEL cells depended on ER stress. We show here for the first time that the inhibition of autophagy induces ER stress...
Source: Apoptosis - August 2, 2016 Category: Molecular Biology Source Type: research

mTOR is a fine tuning molecule in CDK inhibitors-induced distinct cell death mechanisms via PI3K/AKT/mTOR signaling axis in prostate cancer cells
AbstractPurvalanol and roscovitine are cyclin dependent kinase (CDK) inhibitors that induce cell cycle arrest and apoptosis in various cancer cells. We further hypothesized that co-treatment of CDK inhibitors with rapamycin, an mTOR inhibitor, would be an effective combinatory strategy for the inhibition of prostate cancer regard to androgen receptor (AR) status due to inhibition of proliferative pathway, PI3K/AKT/mTOR, and induction of cell death mechanisms. Androgen responsive (AR+), PTEN−/− LNCaP and androgen independent (AR −), PTEN+/ − DU145 prostate cancer cells were exposed to purvalanol (20 ...
Source: Apoptosis - August 2, 2016 Category: Molecular Biology Source Type: research

Synergistic antitumor activity of triple-regulated oncolytic adenovirus with VSTM1 and daunorubicin in leukemic cells
Abstract V - set and transmembrane domain - containing 1 ( VSTM1 ), which is downregulated in bone marrow cells from leukemia patients, may provide a diagnostic and treatment target. Here, a triple-regulated oncolytic adenovirus was constructed to carry a VSTM1 gene expression cassette, SG611-VSTM1, and contained the E1a gene with a 24-nucleotide deletion within the CR2 region under control of the human telomerase reverse transcriptase promoter, E1b gene directed by the hypoxia response element, and VSTM1 gene controlled by the cytomegalovirus promoter. Real-time quantitative PCR and Western blot analyses showed that...
Source: Apoptosis - July 29, 2016 Category: Molecular Biology Source Type: research

GSK-3 β promotes PA-induced apoptosis through changing β-arrestin 2 nucleus location in H9c2 cardiomyocytes
Abstract Palmitic acid (PA), a type of saturated fatty acids, induces cardiovascular diseases by causing cardiomyocyte apoptosis with unclear mechanisms. Akt participates in PA-induced cardiomyocyte apoptosis. GSK-3 β is a substrate of Akt, we investigated its role in PA-induced apoptosis. We reveal that PA inhibits GSK-3β phosphorylation accompanied by inactivation of Akt in H9c2 cardiomyocytes. We also reveal that inhibition the activity of GSK-3β by its inhibitor LiCl or knockdown by siRNA significantly a ttenuates PA-induced cardiomyocyte apoptosis, this suggesting that GSK-3β plays a pro-apoptotic...
Source: Apoptosis - July 18, 2016 Category: Molecular Biology Source Type: research

GSK-3β promotes PA-induced apoptosis through changing β-arrestin 2 nucleus location in H9c2 cardiomyocytes
Abstract Palmitic acid (PA), a type of saturated fatty acids, induces cardiovascular diseases by causing cardiomyocyte apoptosis with unclear mechanisms. Akt participates in PA-induced cardiomyocyte apoptosis. GSK-3β is a substrate of Akt, we investigated its role in PA-induced apoptosis. We reveal that PA inhibits GSK-3β phosphorylation accompanied by inactivation of Akt in H9c2 cardiomyocytes. We also reveal that inhibition the activity of GSK-3β by its inhibitor LiCl or knockdown by siRNA significantly attenuates PA-induced cardiomyocyte apoptosis, this suggesting that GSK-3β plays a pro-apo...
Source: Apoptosis - July 18, 2016 Category: Molecular Biology Source Type: research

Clitocine potentiates TRAIL-mediated apoptosis in human colon cancer cells by promoting Mcl-1 degradation
Abstract Among anti-cancer candidate drugs, TRAIL might be the most specific agent against cancer cells due to its low toxicity to normal cells. Unfortunately, cancer cells usually develop drug resistance to TRAIL, which is a major obstacle for its clinical application. One promising strategy is co-administrating with sensitizer to overcome cancer cells resistance to TRAIL. Clitocine, a natural amino nucleoside purified from wild mushroom, is recently demonstrated that can induce apoptosis in multidrug-resistant human cancer cells by targeting Mcl-1. In the present study,we found that pretreatment with clitocine d...
Source: Apoptosis - July 15, 2016 Category: Molecular Biology Source Type: research

Flavonoids of Rosa roxburghii Tratt exhibit radioprotection and anti-apoptosis properties via the Bcl-2(Ca 2+ )/Caspase-3/PARP-1 pathway
The objective of our study was to assess the radioprotective effect of flavonoids extracted from Rosa roxburghii Tratt (FRT) and investigate the role of Bcl-2(Ca2+)/Caspase-3/PARP-1 pathway in radiation-induced apoptosis. Cells and mice were exposed to 60Co γ-rays at a dose of 6 Gy. The radiation treatment induced significant effects on tissue pathological changes, apoptosis, Ca2+, ROS, DNA damage, and expression levels of Bcl-2, Caspase-3 (C-Caspase-3), and PARP-1. The results showed that FRT acted as an antioxidant, reduced DNA damage, corrected the pathological changes of the tissue induced by radiation, prom...
Source: Apoptosis - July 11, 2016 Category: Molecular Biology Source Type: research

Atorvastatin inhibits the apoptosis of human umbilical vein endothelial cells induced by angiotensin II via the lysosomal-mitochondrial axis
This study was aimed to evaluate lysosomes–mitochondria cross-signaling in angiotensin II (Ang II)-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and whether atorvastatin played a protective role via lysosomal-mitochondrial axis. Apoptosis was detected by flow cytometry, Hoechst 33342 and AO/EB assay. The temporal relationship of lysosomal and mitochondrial permeabilization was established. Activity of Cathepsin D (CTSD) was suppressed by pharmacological and genetic approaches. Proteins production were measured by western blotting. Our study showed that Ang II could induce the apoptosis of HUVEC...
Source: Apoptosis - July 9, 2016 Category: Molecular Biology Source Type: research

Mephebrindole, a synthetic indole analog coordinates the crosstalk between p38MAPK and eIF2 α/ATF4/CHOP signalling pathways for induction of apoptosis in human breast carcinoma cells
Abstract The efficacy of cancer chemotherapeutics is limited by side effects resulting from narrow therapeutic windows between the anticancer activity of a drug and its cytotoxicity. Thus identification of small molecules that can selectively target cancer cells has gained major interest. Cancer cells under stress utilize the Unfolded protein response (UPR) as an effective cell adaptation mechanism. The purpose of the UPR is to balance the ER folding environment and calcium homeostasis under stress. If ER stress is prolonged, tumor cells undergo apoptosis. In the present study we demonstrated an 3,3 ′-(Arylmethylene...
Source: Apoptosis - July 8, 2016 Category: Molecular Biology Source Type: research

Mephebrindole, a synthetic indole analog coordinates the crosstalk between p38MAPK and eIF2α/ATF4/CHOP signalling pathways for induction of apoptosis in human breast carcinoma cells
Abstract The efficacy of cancer chemotherapeutics is limited by side effects resulting from narrow therapeutic windows between the anticancer activity of a drug and its cytotoxicity. Thus identification of small molecules that can selectively target cancer cells has gained major interest. Cancer cells under stress utilize the Unfolded protein response (UPR) as an effective cell adaptation mechanism. The purpose of the UPR is to balance the ER folding environment and calcium homeostasis under stress. If ER stress is prolonged, tumor cells undergo apoptosis. In the present study we demonstrated an 3,3′-(Arylme...
Source: Apoptosis - July 8, 2016 Category: Molecular Biology Source Type: research

Mycobacterium tuberculosis PE13 (Rv1195) manipulates the host cell fate via p38-ERK-NF- κB axis and apoptosis
Abstract PE/PPE family proteins are mycobacteria unique molecules, named after their N-terminal conserved PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains. Mycobacterium tuberculosis (Mtb) PE family gene encoded cell surface proteins are previously reported to be involved in virulence and interaction with host. To explore the role of a novel PE member (PE13, Rv1195), M. smegmatis was used as surrogate host. The study showed that Rv1195 was a cell wall associated protein. Rv1195 can enhance the survival of recombinants under stress conditions such as H 2 O 2 , SDS, low pH. This is largely due to the upregulated transcription o...
Source: Apoptosis - July 1, 2016 Category: Molecular Biology Source Type: research

Melatonin reduces PERK-eIF2 α-ATF4-mediated endoplasmic reticulum stress during myocardial ischemia–reperfusion injury: role of RISK and SAFE pathways interaction
In this study, we performed in vivo and in vitro experiment to investigate the ameliorative effect of melatonin on ER stress with a focus on RISK and SAFE pathways interaction. Male C57Bl/6 m ice received melatonin (300 μg/25 g/day, 3 days before MI/R surgery; 300 μg/25 g, 25 min before the onset of ischemia) pre-treatment with or without the administration of LY294002 (a PI3K/Akt inhibitor), U0126 (an ERK1/2 inhibitor) or AG490 (a STAT3 pathway inhibitor). H9c2 cells were pre-tr eated with melatonin (100 μM, 8 h) in the presence or absence of LY294002, U0126 or AG490. Compa...
Source: Apoptosis - July 1, 2016 Category: Molecular Biology Source Type: research

Advanced oxidative protein products induced human keratinocyte apoptosis through the NOX –MAPK pathway
Abstract Impaired wound healing is a major diabetes-related complication. Keratinocytes play an important role in wound healing. Multiple factors have been proposed that can induce dysfunction in keratinocytes. The focus of present research is at a more specific molecular level. We investigated the role of advanced oxidative protein products (AOPPs) in inducing human immortalized keratinocyte (HaCaT) cell apoptosis and the cellular mechanism underlying the proapoptotic effect of AOPPs. HaCaT cells were treated with increasing concentrations of AOPP –human serum albumin or for increasing time durations. The cell viab...
Source: Apoptosis - July 1, 2016 Category: Molecular Biology Source Type: research