5-Flurouracil disrupts nuclear export and nuclear pore permeability in a calcium dependent manner
AbstractRegulation of nuclear transport is an essential component of apoptosis. As chemotherapy induced cell death progresses, nuclear transport and the nuclear pore complex (NPC) are slowly disrupted and dismantled. 5-Fluorouracil (5-FU) and the camptothecin derivatives irinotecan and topotecan, are linked to altered nuclear transport of specific proteins; however, their general effects on the NPC and transport during apoptosis have not been characterized. We demonstrate that 5-FU, but not topotecan, increases NPC permeability, and disrupts Ran-mediated nuclear transport before the disruption of the NPC. This increased pe...
Source: Apoptosis - December 19, 2016 Category: Molecular Biology Source Type: research

Natural products as modulator of autophagy with potential clinical prospects
AbstractNatural compounds derived from living organisms are well defined for their remarkable biological and pharmacological properties likely to be translated into clinical use. Therefore, delving into the mechanisms by which natural compounds protect against diverse diseases may be of great therapeutic benefits for medical practice. Autophagy, an intricate lysosome-dependent digestion process, with implications in a wide variety of pathophysiological settings, has attracted extensive attention over the past few decades. Hitherto, accumulating evidence has revealed that a large number of natural products are involved in a...
Source: Apoptosis - December 16, 2016 Category: Molecular Biology Source Type: research

Mycobacterium tuberculosis PE_PGRS18 enhances the intracellular survival of M. smegmatis via altering host macrophage cytokine profiling and attenuating the cell apoptosis
AbstractMycobacterium tuberculosis PE/PPE family proteins, named after the presence of conserved PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains at N-terminal, are prevalent inM. tuberculosis genome. The function of most PE/PPE family proteins remains elusive. To characterize the function of PE_PGRS18, the encoding gene was heterologously expressed inM. smegmatis, a nonpathogenic mycobacterium. The recombinant PE_PGRS18 is cell wall associated.M. smegmatis PE_PGRS18 recombinant showed differential response to stresses and altered the production of host cytokines IL-6, IL-1 β, IL-12p40 and IL-10, as well as enhanced surviva...
Source: Apoptosis - December 15, 2016 Category: Molecular Biology Source Type: research

Two coffins and a funeral: early or late caspase activation determines two types of apoptosis induced by DNA damaging agents
AbstractCell cytoskeleton makes profound changes during apoptosis including the organization of an Apoptotic Microtubule Network (AMN). AMN forms a cortical structure which plays an important role in preserving plasma membrane integrity during apoptosis. Here, we examined the cytoskeleton rearrangements during apoptosis induced by camptothecin (CPT), a topoisomerase I inhibitor, in human H460 and porcine LLCPK-1 α cells. Using fixed and living cell imaging, we showed that CPT induced two dose- and cell cycle-dependent types of apoptosis characterized by different cytoskeleton reorganizations, time-dependent caspase a...
Source: Apoptosis - December 9, 2016 Category: Molecular Biology Source Type: research

Cardamonin represses proliferation, invasion, and causes apoptosis through the modulation of signal transducer and activator of transcription 3 pathway in prostate cancer
AbstractThe pleiotropic transcription factor, signal transducer and activator of transcription 3 (STAT3) is often aberrantly activated in a wide variety of cancers and plays a pivotal role in tumor initiation, promotion and progression. Targeting deregulated STAT3 activation by small molecule inhibitors is generally considered as an important therapeutic strategy. Hence, in the present study, we evaluated the potential of cardamonin (CD), a 2 ′,4′-dihydroxy-6′-methoxychalcone, to modulate STAT3 activation in prostate cancer (PC) cells and found that this chalcone can indeed exhibit significant anticancer ...
Source: Apoptosis - November 28, 2016 Category: Molecular Biology Source Type: research

The regulation of the mitochondrial apoptotic pathway by glucocorticoid receptor in collaboration with Bcl-2 family proteins in developing T cells
AbstractGlucocorticoids (GC) are important in the regulation of selection and apoptosis of CD4+CD8+ double-positive (DP) thymocytes. The pronounced GC-sensitivity of DP thymocytes, observed earlier, might be due to the combination of classical (genomic) and alternative (non-genomic) glucocorticoid receptor (GR) signaling events modifying activation or apoptotic pathways. In particular, the previously demonstrated mitochondrial translocation of activated GR in DP thymocytes offered a fascinating explanation for their pronounced GC-induced apoptosis sensitivity. However, the fine molecular details how the mitochondrial trans...
Source: Apoptosis - November 25, 2016 Category: Molecular Biology Source Type: research

A novel 4,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivative inhibits tumor cell invasion and potentiates the apoptotic effect of TNF α by abrogating NF-κB activation cascade
In this study, several novel CBTT derivatives were synthesized and investigated for their possible role as anti-neoplastic agents. The anti-proliferative effect of various CBTT derivatives was analyzed against tumor cell lines by (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. One of the potential CBTT derivative, 5-(3-(2,3-dichlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)flurobenzonitrile (DTTF) was found to be the most potent against cervical cancer SiHa cells and exhibited minimal effect against normal cells. Molecular docking analysis indicated that transcription factor NF- κ...
Source: Apoptosis - November 23, 2016 Category: Molecular Biology Source Type: research

Mille modis morimur : We die in a thousand ways
AbstractDying cells subjected to apoptotic programs are engulfed by neighboring cells or by professional phagocytes, without inflammation or immunological reactions in the tissue where apoptosis takes place. Apoptotic cells release danger-associated project signals to their neighbours, through different molecular patterns, stimulate antigen production and immune responses. Microenvironmental effects with several functional consequences indicate that cell death is a complex process and may take place in several ways. This idea is expressed by the title of the Special Issue and by the title of the guest editorial “Mill...
Source: Apoptosis - November 22, 2016 Category: Molecular Biology Source Type: research

HSP90 is a promising target in gemcitabine and 5-fluorouracil resistant pancreatic cancer
AbstractChemotherapy (CT) options in pancreatic cancer (PC) are limited to gemcitabine and 5-fluorouracil (5-FU). Several identified molecular targets in PC represent client proteins of HSP90. HSP90 is a promising target since it interferes with many oncogenic signaling pathways simultaneously. The aim of this study was to evaluate the efficacy of different HSP90 inhibitors in gemcitabine and 5-FU resistant PC. PC cell lines 5061, 5072 and 5156 were isolated and brought in to culture from patients being operated at our institution. L3.6pl cell line served as a control. Anti-proliferative efficacy of three different HSP90 i...
Source: Apoptosis - November 21, 2016 Category: Molecular Biology Source Type: research

DMFC (3,5-dimethyl- 7 H-furo[3,2-g]chromen-7-one) regulates Bim to trigger Bax and Bak activation to suppress drug-resistant human hepatoma
In this study, we aimed at elucidating the molecular mechanisms underlying DMFC anti-cancer activity and determining whether DMFC is effective in suppression of drug-resistant human hepatocellular carcinoma. We show here that DMFC effectively suppresses both the parent and the multidrug-resistant hepatoma cell growth in vitro and DMFC suppresses hepatoma cell growth at least in part through inducing tumor cell apoptosis. In the molecular level, we observed that DMFC treatment decreases Bcl-2 level by a post-transcriptional mechanism and activates Bim transcription to increase Bim mRNA and protein level in hepatoma cells. F...
Source: Apoptosis - November 20, 2016 Category: Molecular Biology Source Type: research

Heme oxygenase-1 protects spinal cord neurons from hydrogen peroxide-induced apoptosis via suppression of Cdc42/MLK3/MKK7/JNK3 signaling
AbstractThe mechanisms by which oxidative stress induces spinal cord neuron death has not been completely understood. Investigation on the molecular signal pathways involved in oxidative stress-mediated neuronal death is important for development of new therapeutics for oxidative stress-associated spinal cord disorders. In current study we examined the role of heme oxygenase-1 (HO-1) in the modulation of MLK3/MKK7/JNK3 signaling, which is a pro-apoptotic pathway, after treating primary spinal cord neurons with H2O2. We found that MLK3/MKK7/JNK3 signaling was substantially activated by H2O2 in a time-dependent manner, demon...
Source: Apoptosis - November 17, 2016 Category: Molecular Biology Source Type: research

Advanced oxidation protein products induce chondrocyte death through a redox-dependent, poly (ADP-ribose) polymerase-1-mediated pathway
This study aimed to investigate the effect of AOPPs on apoptosis in human chondrocytes. Chondrocytes were treated with AOPPs. Cell death, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, reactive oxygen species (ROS) generation, and the expression of apoptotic proteins were detected in vitro. AOPPs levels were detected by colorimetric method. The results in vitro demonstrated that AOPPs induced cell death in human chondrocyte through a redox-dependent pathway, including RAGE-mediated, NADPH oxidase-dependent ROS generation, and poly (ADP-ribose) polymerase-1 (PARP-1) activation. Targeting AOPPs-induced...
Source: Apoptosis - November 16, 2016 Category: Molecular Biology Source Type: research

Knockdown of KLF11 attenuates hypoxia/reoxygenation injury via JAK2/STAT3 signaling in H9c2
AbstractKLF11 is aKr üppel-like factor (KLF) family member, which plays a central role in cardiac hypertrophy and cerebrovascular protection during ischemic insults. However, the roles of KLF11 in hypoxia/reoxygenation (H/R) injury of rat cardiomyocytes H9c2 have not been elucidated. The aim of this study was to evaluate the effects of KLF11 on H/R injury and investigate the molecular mechanisms involved. Here, we found that KLF11 was increased following H/R and reached the highest level with 24  h hypoxia followed by 12 h reoxygenation. Moreover, we found that inhibition of KLF11 by small RNA suppressed cel...
Source: Apoptosis - November 14, 2016 Category: Molecular Biology Source Type: research

NEDD4-1 protects against ischaemia/reperfusion-induced cardiomyocyte apoptosis via the PI3K/Akt pathway
AbstractActivation of the Akt pathway has been shown to protect the heart from ischaemia/reperfusion (I/R) injury. NEDD4-1 has been shown to positively regulate nuclear trafficking of the activated form of Akt. However, the role of NEDD4-1 in cardiac I/R injury remains to be elucidated. In the present study, Lentiviral vectors were constructed to overexpress or knockdown NEDD4-1 in H9c2 cardiomyocytes subjected to I/R injury or ischemic preconditioning (IPC). The results indicated that NEDD4-1 levels were decreased after I/R and increased after IPC in rat heart tissue and in H9c2 cardiomyocytes. Overexpression of NEDD4-1 a...
Source: Apoptosis - November 10, 2016 Category: Molecular Biology Source Type: research

Effects of clary sage oil and its main components, linalool and linalyl acetate, on the plasma membrane of Candida albicans : an in vivo EPR study
AbstractThe effects of clary sage (Salvia sclarea L.) oil (CS-oil), and its two main components, linalool (Lol) and linalyl acetate (LA), on cells of the eukaryotic human pathogen yeast Candida albicans were studied. Dynamic and thermodynamic properties of the plasma membrane were investigated by electron paramagnetic resonance (EPR) spectroscopy, with 5-doxylstearic acid (5-SASL) and 16-SASL as spin labels. The monitoring of the head group regions with 5-SASL revealed break-point frequency decrease in a temperature dependent manner of the plasma membrane between 9.55 and 13.15  °C in untreated, in CS-oil-, Lol-...
Source: Apoptosis - November 7, 2016 Category: Molecular Biology Source Type: research

Presence of encircling granulosa cells protects against oxidative stress-induced apoptosis in rat eggs cultured in vitro
AbstractIncreased oxidative stress (OS) due to in vitro culture conditions can affect the quality of denuded eggs during various assisted reproductive technologies (ARTs). Presence of intact granulosa cells may protect eggs from OS damage under in vitro culture conditions. The present study was aimed to investigate whether encircling granulosa cells could protect against hydrogen peroxide (H2O2)-induced egg apoptosis in ovulated cumulus oocyte complexes (COCs) cultured in vitro. The OS was induced by exposing COCs as well as denuded eggs with various concentrations of H2O2 for 3  h in vitro. The morphological changes,...
Source: Apoptosis - November 4, 2016 Category: Molecular Biology Source Type: research

The role of endoplasmic reticulum stress in neurodegenerative disease
AbstractThe endoplasmic reticulum (ER) is an important organelle involved in cellular homeostasis and control of protein quality. Unfolded protein response (UPR) is a cellular response to ER stress and promotes cell survival. Severe or prolonged stress activates apoptosis signaling to trigger cell death. In mammals, the UPR is initiated by three major ER stress sensors, including inositol-requiring transmembrane kinase 1, double-stranded RNA-activated protein kinase-like ER kinase and activating transcription factor 6. UPR dysfunction plays an important role in the pathogenesis of neurodegenerative diseases including Alzhe...
Source: Apoptosis - November 3, 2016 Category: Molecular Biology Source Type: research

Apoptosis-induced lymphopenia in sepsis and other severe injuries
AbstractSepsis and other acute injuries such as severe trauma, extensive burns, or major surgeries, are usually followed by a period of marked immunosuppression. In particular, while lymphocytes play a pivotal role in immune response, their functions and numbers are profoundly altered after severe injuries. Apoptosis plays a central role in this process by affecting immune response at various levels. Indeed, apoptosis-induced lymphopenia duration and depth have been associated with higher risk of infection and mortality in various clinical settings. Therapies modulating apoptosis represent an interesting approach to restor...
Source: Apoptosis - November 2, 2016 Category: Molecular Biology Source Type: research

Reduced risk of apoptosis: mechanisms of stress responses
AbstractApoptosis signaling pathways are integrated into a wider network of interconnected apoptotic and anti-apoptotic pathways that regulate a broad range of cell responses from cell death to growth, development and stress responses. An important trigger for anti- or pro-apoptotic cell responses are different forms of stress including hypoxia, energy deprivation, DNA damage or inflammation. Stress duration and intensity determine whether the cell ’s response will be improved cell survival, due to stress adaptation, or cell death by apoptosis, necrosis or autophagy. Although the interplay between enhanced stress tol...
Source: Apoptosis - November 1, 2016 Category: Molecular Biology Source Type: research

Increased levels of RNA oxidation enhance the reversion frequency in aging pro-apoptotic yeast mutants
AbstractDespite recent advances in understanding the complexity of RNA processes, regulation of the metabolism of oxidized cellular RNAs and the mechanisms through which oxidized ribonucleotides affect mRNA translation, and consequently cell viability, are not well characterized. We show here that the level of oxidized RNAs is markedly increased in a yeast decappingKllsm4 Δ1 mutant, which accumulates mRNAs, ages much faster that the wild type strain and undergoes regulated-cell-death. We also found that inKllsm4 Δ1 cells the mutation rate increases during chronological life span indicating that the capacity to ...
Source: Apoptosis - October 31, 2016 Category: Molecular Biology Source Type: research

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 24, 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 23, 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 21, 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 21, 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 20, 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 20, 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 19, 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 18, 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 18, 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 17, 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 16, 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 12, 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 12, 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 11, 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 6, 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 3, 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 3, 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 - September 30, 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 28, 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 25, 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 22, 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 21, 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 20, 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 19, 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 19, 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 14, 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 - August 31, 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 - August 31, 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 22, 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 19, 2016 Category: Molecular Biology Source Type: research