KH-TFMDI, a novel sirtuin inhibitor, alters the cytoskeleton and mitochondrial metabolism promoting cell death in Leishmania amazonensis
AbstractTreatment of leishmaniasis involves the use of antimonials, miltefosine, amphotericin B or pentamidine. However, the side effects of these drugs and the reports of drug-resistant parasites demonstrate the need for new treatments that are safer and more efficacious. Histone deacetylase inhibitors are a new class of compounds with potential to treat leishmaniasis. Herein, we evaluated the effects of KH-TFMDI, a novel histone deacetylase inhibitor, onLeishmania amazonensis promastigotes and intracellular amastigotes. The IC50 values of this compound for promastigotes and intracellular amastigotes were 1.976 and 1.148 ...
Source: Apoptosis - July 6, 2017 Category: Molecular Biology Source Type: research

Bisdemethoxycurcumin sensitizes cisplatin-resistant lung cancer cells to chemotherapy by inhibition of CA916798 and PI3K/AKT signaling
This study aimed to assess the effects of curcumin on regulating chemosensitivity in cisplatin-resistant non-small cell lung cancer (NSCLC) cells in vitro and to explore the underlying molecular mechanisms. Human cisplatin-sensitive A549 and cisplatin-resistant A549/CDDP lung adenocarcinoma cells were treated with curcumin to assess cell viability and gene modulations using quantitative reverse transcription –polymerase chain reaction (qRT-PCR) and western blotting. CA916798 shRNA and point mutations were used to assess the CA916798 functions and phosphorylation sites. Bisdemethoxycurcumin sensitized cisplatin-resist...
Source: Apoptosis - July 4, 2017 Category: Molecular Biology Source Type: research

Structural aspects of transglutaminase 2: functional, structural, and regulatory diversity
AbstractTransglutaminase 2 (TG2) is a multi-functional protein that has both protein cross-linking and guanosine 5 ′-triphosphate (GTP) hydrolysis activities. The activities of this protein are controlled by many cellular factors, including calcium (Ca2+) and GTP, and have been implicated in several physiological activities, including apoptosis, angiogenesis, wound healing, cellular differentiation, neuronal regeneration, and bone development. TG2 is linked to many human diseases such as inflammatory disease, celiac disease, neurodegenerative disease, diabetes, tissue fibrosis, and various cancers and is one of the m...
Source: Apoptosis - July 4, 2017 Category: Molecular Biology Source Type: research

Amelioration of bleomycin-induced pulmonary fibrosis by chlorogenic acid through endoplasmic reticulum stress inhibition
AbstractTo investigate the inhibitory effects of chlorogenic acid on pulmonary fibrosis and the internal mechanisms in vivo and in vitro. 30 male BALB/C mice were randomized into 5 groups: control group, pulmonary fibrosis model group, low, middle and high dose of chlorogenic acid groups. Mice in pulmonary fibrosis model group were administered 5.0  mg/kg bleomycin with intracheal instillation and mice in 3 chlorogenic acid groups were treated with chlorogenic acid every day for 28 days after bleomycin administration. Lung tissue histology was observed using HE staining. Primary pulmonary fibroblasts were isolated and...
Source: Apoptosis - July 4, 2017 Category: Molecular Biology Source Type: research

Astragalus polysaccharides inhibits cell growth and pro-inflammatory response in IL-1 β-stimulated fibroblast-like synoviocytes by enhancement of autophagy via PI3K/AKT/mTOR inhibition
This study demonstrated that administration of APS dose-dependently impaired cell viability, increased cell apoptosis by decreasing Bcl-2 expression, increasing Bax expression and Caspase3 activity in IL-1 β-stimulated RSC-364 cells and RA-FLS. Simultaneously, IL-1β-induced production of pro-inflammatory cytokines IL-6 and TNF-α was significantly decreased after APS treatment. Furthermore, preconditioning with APS dramatically enhanced autophagy activity by increasing Beclin-1 and LC3II/LC3I expres sion coupled with decreasing p62 expression and augmenting the number of LC3 puncta in IL-1β-stimulated R...
Source: Apoptosis - June 28, 2017 Category: Molecular Biology Source Type: research

Acquisition of anoikis resistance promotes alterations in the Ras/ERK and PI3K/Akt signaling pathways and matrix remodeling in endothelial cells
This study investigates the possible involvement of ECM components and signaling pathways in the regulation of resistance to anoikis in endothelial cells (EC). Endothelial cells submitted to stressful conditions by blocking adhesion to substrate (anoikis resistance) display an up-regulation of Ras/ERK and PI3k/Akt pathways by high expression of Ras, ERK, PI3K (p110 α) and Akt (Thr 308). After ERK and PI3K inhibiting, all EC-derived cell lines studied showed lower growth, a decrease in invasive potential and a higher rate of apoptosis. Furthermore, anoikis-resistant cell lines display a decrease in the expression of f...
Source: Apoptosis - June 26, 2017 Category: Molecular Biology Source Type: research

Multi-targeted therapy of everolimus in Kaposi ’s sarcoma associated herpes virus infected primary effusion lymphoma
In this study, we evaluated the e fficacy of everolimus, an mTOR inhibitor in inducing apoptosis of PEL cells. Dose-dependent treatment of everolimus triggered mitochondria-mediated caspase-dependent apoptosis in PEL cells. Everolimus downregulated KSHV latent antigen expression with concurrent blocking of lytic reactivation for act ive virus replication. Everolimus also inhibited latent antigen mediated constitutively active STAT-3 and NF-κB signalling. We co-cultured everolimus treated PEL cells with immature dendritic cells and found activation of dendritic cells with increase in surface expression of CD86 and HLA...
Source: Apoptosis - June 26, 2017 Category: Molecular Biology Source Type: research

Fluoxetine induces apoptosis through endoplasmic reticulum stress via mitogen-activated protein kinase activation and histone hyperacetylation in SK-N-BE(2)-M17 human neuroblastoma cells
In this study, the molecular mechanisms underlying the anti-cancer effects of FLX were investigated in SK-N-BE(2)-M17 human neuroblastoma cells. FLX induced apoptotic cell death, activation of caspase-4, -9, and -3, and expression of endoplasmic reticulum (ER) stress-associated proteins, including C/EBP homologous protein (CHOP). Inhibition of ER stress by treatment with the ER stress inhibitors, salubrinal and 4-phenylbutyric acid or CHOP siRNA transfection reduced FLX-induced cell death. FLX induced phosphorylation of mitogen-activated protein kinases (MAPKs) family, p38, JNK, and ERK, and an upstream kinase apoptosis si...
Source: Apoptosis - June 24, 2017 Category: Molecular Biology Source Type: research

AMPK is activated early in cerebellar granule cells undergoing apoptosis and influences VADC1 phosphorylation status and activity
AbstractThe neurodegeneration of cerebellar granule cells, after low potassium induced apoptosis, is known to be temporally divided into an early and a late phase. Voltage-dependent anion channel-1 (VDAC1) protein, changing from the closed inactive state to the active open state, is central to the switch between the early and late phase. It is also known that: (i) VDAC1 can undergo phosphorylation events and (ii) AMP-activated protein kinase (AMPK), the sensor of cellular stress, may have a role in neuronal homeostasis. In the view of this, the involvement of AMPK activation and its correlation with VDAC1 status and activi...
Source: Apoptosis - June 22, 2017 Category: Molecular Biology Source Type: research

Genetic variants in cell death pathway genes and HBV-related hepatocellular carcinoma among a Chinese Han population
AbstractCell death pathway plays an important role in apoptosis, and corruption of this signaling pathway has been shown to participate in carcinogenesis. We aimed at determining whether genetic variants in CASP8, CASP10 and CFLAR influence the development and clinical outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A hospital-based case-control study, including 600 HCC cases and 600 HBsAg positive controls without HCC, was conducted to assess the relationship between 11 tagging SNPs in CASP8, CASP10 and CFLAR and HBV-related HCC risk and prognosis in a Chinese Han population. Among the 11 polym...
Source: Apoptosis - June 22, 2017 Category: Molecular Biology Source Type: research

Urokinase plasminogen activator protects cardiac myocytes from oxidative damage and apoptosis via hOGG1 induction
AbstractThe role of uPA in tissue remodeling and cell migration is already well established. In addition, uPA was reported to stabilize p53, a key cell cycle control, DNA repair and apoptosis initiation protein. We aimed to determine the role of uPA-uPAR signaling towards cell survival or apoptosis in human adult cardiac myocytes (HACM). HACM were stimulated with uPA and DNA damage was inflicted by incubating cells with 200  µM H2O2. To analyze for apoptotic cells we applied TUNEL staining. Oxidative damage foci were analyzed by staining for 8-oxoguanine base pairs. In vivo qPCR analysis from RNA extracted from ...
Source: Apoptosis - June 22, 2017 Category: Molecular Biology Source Type: research

Phosphatidylethanolamine targeting for cell death imaging in early treatment response evaluation and disease diagnosis
AbstractPhosphatidylethanolamine (PE) is one of the most abundant phospholipids in mammalian plasma membranes. In healthy cells, PE resides predominantly in the inner leaflet of the cell membrane. In dead or dying cells on the other hand, PE is externalized to the outer leaflet of the plasma membrane. The exposure of PE on the cell surface has therefore become an attractive target for the molecular imaging of cell death using single-photon emission computed tomography (SPECT) and positron emission tomography (PET). This has motivated the development of PE-specific probes to measure cell death in vitro and non-invasively in...
Source: Apoptosis - June 16, 2017 Category: Molecular Biology Source Type: research

Perifosine enhances bevacizumab-induced apoptosis and therapeutic efficacy by targeting PI3K/AKT pathway in a glioblastoma heterotopic model
In conclusion, BVZ plus PRF renders a paramount proapoptotic effect, leading to a major therapeutic efficacy and might be a new substitute for GBM therapy in the clinic. (Source: Apoptosis)
Source: Apoptosis - June 14, 2017 Category: Molecular Biology Source Type: research

Dihydromyricetin protects human umbilical vein endothelial cells from injury through ERK and Akt mediated Nrf2/HO-1 signaling pathway
In this study, we used an ox-LDL injured human umbilical vein endothelial cell (HUVEC) in vitro model to explore the protective effects and mechanism of DMY. HUVECs were pretreatment with DMY and then exposed to ox-LDL, the cell viability was measured. Then, the anti-oxidative enzymes were tested by commercial kits and intracellular reactive oxygen species (ROS) was measured by flow cytometry, cell apoptosis was determined by Annexin-V/PI assay and apoptosis-related proteins were detected by western blot. Our results showed that DMY pretreatment provided cytoprotective effects by suppressing ox-LDL-induced endothelial cell...
Source: Apoptosis - June 13, 2017 Category: Molecular Biology Source Type: research

Fludarabine inhibits STAT1-mediated up-regulation of caspase-3 expression in dexamethasone-induced osteoblasts apoptosis and slows the progression of steroid-induced avascular necrosis of the femoral head in rats
This study assessed the effects of fludarabine in vitro (primary murine osteoblasts) and in vivo (rat SANFH model). In vitro, pretreatment with fludarabine significantly inhibited Dexamethasone (Dex)-induced apoptosis in osteoblasts, which was examined by TUNEL staining. Treatment with Dex caused a remarkable decrease in the expression of Bcl-2; an increase in cytochrome c release; activation of BAX, caspase-9, and caspase-3; and an obvious enhancement in STAT1 phosphorylation. However, treatment resulted in the up-regulation of caspase-3 expression. Enhanced P-STAT1 activity and up-regulation of caspase-3 expression were ...
Source: Apoptosis - June 10, 2017 Category: Molecular Biology Source Type: research

Diallyl trisulfide ameliorates myocardial ischemia –reperfusion injury by reducing oxidative stress and endoplasmic reticulum stress-mediated apoptosis in type 1 diabetic rats: role of SIRT1 activation
AbstractDiallyl trisulfide (DATS) protects against apoptosis during myocardial ischemia-reperfusion (MI/R) injury in diabetic state, although the underlying mechanisms remain poorly defined. Previously, we and others demonstrated that silent information regulator 1 (SIRT1) activation inhibited oxidative stress and endoplasmic reticulum (ER) stress during MI/R injury. We hypothesize that DATS reduces diabetic MI/R injury by activating SIRT1 signaling. Streptozotocin (STZ)-induced type 1 diabetic rats were subjected to MI/R surgery with or without perioperative administration of DATS (40  mg/kg). We found that DATS trea...
Source: Apoptosis - June 2, 2017 Category: Molecular Biology Source Type: research

AP-2 α reverses vincristine-induced multidrug resistance of SGC7901 gastric cancer cells by inhibiting the Notch pathway
In conclusion, our results indicate that AP-2α can reverse the MDR of gastric cancer cells, which may be realized by inhibiting the Notch signaling pathway. (Source: Apoptosis)
Source: Apoptosis - June 2, 2017 Category: Molecular Biology Source Type: research

Role of a novel benzoxazine derivative in the chemosensitization of colon cancer
In this study, the chemosensitizing potential of a novel benzoxazine derivative in combination with Doxorubicin, a DNA damaging chemotherapeutic drug was evaluated. The results of this study showed that the compound LTUR6 is a potent chemosensitizer of Doxorubicin in colon cancer cell lines, HCT116 and HT29. It was also observed that LTUR6 delayed the resolution of Doxorubicin-induced γH2AX, a specific marker of unrepaired DNA DSB, and prolonged cell cycle arrest in both cell lines. This eventually led to DNA fragmentation, caspase activation and ultimately apoptosis in LTUR6 treated cell lines. Results of western bl...
Source: Apoptosis - June 2, 2017 Category: Molecular Biology Source Type: research

Augmenter of liver regeneration regulates autophagy in renal ischemia –reperfusion injury via the AMPK/mTOR pathway
AbstractAutophagy may have protective effects in renal ischemia –reperfusion (I/R) injury, although the underlying mechanisms remain unclear. Augmenter of liver regeneration (ALR), a widely distributed multifunctional protein that is originally identified as a hepatic growth factor, may participate in the process of autophagy. To investigate the role of ALR in autophagy, ALR expression is knocked-down in human kidney 2 (HK-2) cells with short hairpin RNA lentivirals. Then, the level of autophagy is measured in the shRNA/ALR group and the shRNA/control group in an in vitro model of ischemia–reperfusion (I/R). Th...
Source: Apoptosis - May 2, 2017 Category: Molecular Biology Source Type: research

The mechanism of Jurkat cells apoptosis induced by Aggregatibacter actinomycetemcomitans cytolethal distending toxin
AbstractCytolethal distending toxin (CDT) which is produced byAggregatibacter actinomycetemcomitans causes apoptosis in lymphocytes. But the specific mechanism is not clear. The aim of our research was to investigate the effect and mechanism during this process. The wild-type CdtA, CdtB, CdtC (CdtAW, CdtBW, CdtCW) and mutant CdtB (CdtBM) were expressed and purified respectively and the purity of each subunit was examined by BandScan software. And the type I deoxyribonuclease and PI-3,4,5-triphosphate (PI-3,4,5-P3, PIP3) phosphatase activity were detected by DNA agarose gel electrophoresis and enzyme-linked immunosorbent as...
Source: Apoptosis - April 23, 2017 Category: Molecular Biology Source Type: research

Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs)
AbstractInhibitors of apoptosis (IAPs) are a family of proteins that play a significant role in the control of programmed cell death (PCD). PCD is essential to maintain healthy cell turnover within tissue but also to fight disease or infection. Uninhibited, IAPs can suppress apoptosis and promote cell cycle progression. Therefore, it is unsurprising that cancer cells demonstrate significantly elevated expression levels of IAPs, resulting in improved cell survival, enhanced tumor growth and subsequent metastasis. Therapies to target IAPs in cancer has garnered substantial scientific interest and as resistance to anti-cancer...
Source: Apoptosis - April 19, 2017 Category: Molecular Biology Source Type: research

Role of glycogen synthase kinase following myocardial infarction and ischemia –reperfusion
AbstractGlycogen synthase kinase-3 beta (GSK3 β) is principally is a glycogen synthase phosphorylating enzyme that is well known for its role in muscle metabolism. GSK3β is a serine/threonine protein Kinase, which is responsible for several essential roles in mammalian cells. This enzyme is implicated in the pathophysiology of many conditions involved in homeostasis and cellular immigration. GSK3β is involved in several pathways leading to neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Increasing evidence has shown the potential importance of GSK3β in ischemi...
Source: Apoptosis - April 18, 2017 Category: Molecular Biology Source Type: research

Retraction Note to: Advanced oxidation protein products induce chondrocyte death through a redox-dependent, poly(ADP-ribose) polymerase-1-mediated pathway
(Source: Apoptosis)
Source: Apoptosis - April 18, 2017 Category: Molecular Biology Source Type: research

Alcohol and thiamine deficiency trigger differential mitochondrial transition pore opening mediating cellular death
This study indicates two different mitochondria pathways regulating cellular death: The first mechanism may engage alcohol which activates the c-subunit ring of the F0-ATP synthase to form MPT pore-dependent apoptosis; following the second mechanism, TD activates CyP-D translocation from mitochondrial matrix towards the mitochondrial inner membrane to form MPT pore-dependent necrosis. These studies shed light upon molecular and cellular mechanisms underlying apoptosis and necrosis in developemental brain disorders related to alcohol and thiamine deficiency, in hopes of developing new therapeutic strategies for FAS medicati...
Source: Apoptosis - April 17, 2017 Category: Molecular Biology Source Type: research

Pro-apoptotic signaling induced by Retinoic acid and dsRNA is under the control of Interferon Regulatory Factor-3 in breast cancer cells
AbstractBreast cancer is one of the most lethal malignancies for women. Retinoic acid (RA) and double-stranded RNA (dsRNA) are considered signaling molecules with potential anticancer activity. RA, co-administered with the dsRNA mimic polyinosinic –polycytidylic acid (poly(I:C)), synergizes to induce a TRAIL (Tumor-Necrosis-Factor Related Apoptosis-Inducing Ligand)- dependent apoptotic program in breast cancer cells. Here, we report that RA/poly(I:C) co-treatment, synergically, induce the activation of Interferon Regulatory Factor-3 (IRF3) in breast cancer cells. IRF3 activation is mediated by a member of the pathoge...
Source: Apoptosis - April 13, 2017 Category: Molecular Biology Source Type: research

Study on the apoptosis mediated by cytochrome c and factors that affect the activation of bovine longissimus muscle during postmortem aging
This study investigates whether bovine longissimus muscle cell apoptosis occurs during postmortem aging and whether apoptosis is dependent on the mitochondria pathway. This study also determines the apoptosis process mediated by cytochrome c after its release from mitochondria and the factors that affect the activation processes. Results indicate that apoptotic nuclei were detected at 12  h postmortem. Cytochrome c release from the mitochondria to the cytoplasm activated the caspase-9 and caspase-3 at early postmortem aging and the activation of caspase-9 occurs before the activation of caspase-3. The pH level decreas...
Source: Apoptosis - April 12, 2017 Category: Molecular Biology Source Type: research

Novel Triazole linked 2-phenyl benzoxazole derivatives induce apoptosis by inhibiting miR-2, miR-13 and miR-14 function in Drosophila melanogaster
In this study, we have identified novel Triazole linked 2-phenyl benzoxazole derivatives (13j and 13h) as a negative regulator of apoptosis inhibiting micro RNAs (miR-2, miR-13 and miR-14) in a well established in vivo modelDrosophila melanogaster where the process of apoptosis is very similar to human apoptosis. These compounds inhibitmiR-2, miR-13 andmiR-14 activity at their target sites, which induce an increased caspase activity, and in turn influence the caspase dependent apoptotic pathway. These two compounds also increase the mitochondrial reactive oxygen species  (ROS) level to trigger apoptotic cell death. (Source: Apoptosis)
Source: Apoptosis - April 11, 2017 Category: Molecular Biology Source Type: research

PERK signalling pathway mediates single prolonged stress-induced dysfunction of medial prefrontal cortex neurons
AbstractPost-traumatic stress disorder (PTSD) is characterized with abnormal learning and memory. Impairments in learning and memory are closely associated with apoptosis in the medial prefrontal cortex (mPFC). We previously examined the endoplasmic reticulum (ER) stress was involved in the apoptosis in the mPFC of PTSD. The PERK pathway plays the important role in the ER stress-induced apoptosis. The aim of the present study was to explore the role of PERK pathway in neuronal apoptosis in the mPFC of rat models of PTSD. We used the single prolonged stress (SPS) to mimic PTSD in rats and studied the effects of the PERK pat...
Source: Apoptosis - April 8, 2017 Category: Molecular Biology Source Type: research

Fatty acid synthase regulates the chemosensitivity of breast cancer cells to cisplatin-induced apoptosis
AbstractFatty acid synthase (FASN) is a key enzyme in fat biosynthesis that is over-expressed in advanced breast cancer stages. Cisplatin (CDDP) is a platinum-based drug used in the treatment of certain types of this disease. Although it was shown that FASN inhibition induced apoptosis by enhancing the cytotoxicity of certain drugs in breast cancer, its role in regulating the chemosensitivity of different types of breast cancer cells to CDDP-induced apoptosis is not established yet. Therefore, two different breast cancer cell lines; triple negative breast cancer (TNBC; MDA-MB-231) and triple positive breast cancer (TPBC; B...
Source: Apoptosis - April 6, 2017 Category: Molecular Biology Source Type: research

Relaxin attenuates aristolochic acid induced human tubular epithelial cell apoptosis in vitro by activation of the PI3K/Akt signaling pathway
AbstractAristolochic acid nephropathy remains a leading cause of chronic kidney disease (CKD), however few treatment strategies exist. Emerging evidence has shown that H2 relaxin (RLX) possesses powerful antifibrosis and anti-apoptotic properties, therefore we aimed to investigate whether H2 relaxin  can be employed to reduce AA-induced cell apoptosis. Human proximal tubular epithelial (HK-2) cells exposed to AA-I were treated with or without administration of H2 RLX. Cell viability was examined using the WST-8 assay. Apoptotic morphologic alterations were observed using the Hoechst 33342 stai ning method. Apoptosis w...
Source: Apoptosis - April 6, 2017 Category: Molecular Biology Source Type: research

Notch-4 silencing inhibits prostate cancer growth and EMT via the NF- κB pathway
AbstractEpithelial-mesenchymal transition (EMT) is implicated in the metastasis of human prostate cancer (PCa). Notch signaling has been established as a regulator of EMT. Notch-4 has emerged as a mammary proto-oncogene and a target in several cancers. However, the role and the mechanism of action of Notch-4 in PCa are still unclear. In the present study, we first observed a marked increase in Notch-4 expression in the PCa cell lines DU145, PC3 and LnCAP compared with the non-malignant prostate epithelial cell line RWPE1. Knocking down the expression of Notch-4 suppressed the viability and proliferation in the PCa cell lin...
Source: Apoptosis - April 3, 2017 Category: Molecular Biology Source Type: research

EGCG protects against homocysteine-induced human umbilical vein endothelial cells apoptosis by modulating mitochondrial-dependent apoptotic signaling and PI3K/Akt/eNOS signaling pathways
In conclusion, the present study shows that EGCG prevents Hcy-induced HUVECs apoptosis via modulating mitochondrial apoptotic and PI3K/Akt/eNOS signaling pathways. Furthermore, the results indicate that EGCG is likely to represent a potential therapeutic strategy for atherosclerosis associated with Hyperhomocysteinemia (HHcy). (Source: Apoptosis)
Source: Apoptosis - March 18, 2017 Category: Molecular Biology Source Type: research

Microglia activation contributes to quinolinic acid-induced neuronal excitotoxicity through TNF- α
AbstractIt has been reported that activation of NF- κB is involved in excitotoxicity; however, it is not fully understood how NF-κB contributes to excitotoxicity. The aim of this study is to investigate if NF-κB contributes to quinolinic acid (QA)-mediated excitotoxicity through activation of microglia. In the cultured primary cortical neurons and microglia BV-2 cells, the effects of QA on cell survival, NF-κB expression and cytokines production were investigated. The effects of BV-2-conditioned medium (BCM) on primary cortical neurons were examined. The effects of pyrrolidine dithiocarbamate (PDTC)...
Source: Apoptosis - March 16, 2017 Category: Molecular Biology Source Type: research

Ricolinostat, a selective HDAC6 inhibitor, shows anti-lymphoma cell activity alone and in combination with bendamustine
AbstractHistone deacetylase inhibitors (HDACis) have emerged as a new class of anticancer agents, targeting the biological process including cell cycle and apoptosis. We investigated and explained the anticancer effects of an HDAC6 inhibitor, ricolinostat alone and in combination with bendamustine in lymphoma cell lines. Cell viability was measured by MTT assay. Apoptosis, reactive oxygen species (ROS) generation, Bcl-2 protein expression, cell cycle progression and tubuline expression were determined by flow cytometry. The effects of ricolinostat alone and in combination on the caspases, PI3K/Akt, Bcl-2 pathways, ER stres...
Source: Apoptosis - March 16, 2017 Category: Molecular Biology Source Type: research

A novel non-ATP competitive FGFR1 inhibitor with therapeutic potential on gastric cancer through inhibition of cell proliferation, survival and migration
AbstractFibroblast growth factor receptor 1 (FGFR1), belonging to receptor tyrosine kinases (RTKs), possesses various biological functions. Over-expression of FGFR1 has been observed in multiple human malignancies. Hence, targeting FGFR1 is an attractive prospect for the advancement of cancer treatment options. Here, we present a novel small molecular FGFR1 inhibitor L16H50, which can inhibit FGFR1 kinase in an ATP-independent manner. It potently inhibits FGFR1-mediated signaling in a gastric cancer cell line, resulting in inhibition of cell growth, survival and migration. It also displays an outstanding anti-tumor activit...
Source: Apoptosis - March 16, 2017 Category: Molecular Biology Source Type: research

Changes in membrane lipids drive increased endocytosis following Fas ligation
AbstractOnce activated, some surface receptors promote membrane movements that open new portals of endocytosis, in part to facilitate the internalization of their activated complexes. The prototypic death receptor Fas (CD95/Apo1) promotes a wave of enhanced endocytosis that induces a transient intermixing of endosomes with mitochondria in cells that require mitochondria to amplify death signaling. This initiates a global alteration in membrane traffic that originates from changes in key membrane lipids occurring in the endoplasmic reticulum (ER). We have focused the current study on specific lipid changes occurring early a...
Source: Apoptosis - March 14, 2017 Category: Molecular Biology Source Type: research

RIPK1/RIPK3/MLKL-mediated necroptosis contributes to compression-induced rat nucleus pulposus cells death
AbstractThe aim of this study was to systematically investigate the role of necroptosis in compression-induced rat nucleus pulposus (NP) cells death, as well as explore the underlying mechanisms involved. Rat NP cells underwent various periods of exposure to 1.0  MPa pressure. Cell viability and cell death were quantified by using cell counting kit-8 (CCK-8), and Calcein-AM/propidium iodine (PI) staining respectively. Necroptosis-associated target molecules receptor-interacing protein kinase 1 (RIPK1), phosphorylated RIPK1 (pRIPK1), receptor-interacing pro tein kinase 3 (RIPK3), phosphorylated RIPK3 (pRIPK3) and mixed...
Source: Apoptosis - March 12, 2017 Category: Molecular Biology Source Type: research

CF 3 DODA-Me induces apoptosis, degrades Sp1, and blocks the transformation phase of the blebbishield emergency program
AbstractCancer stem cells are capable of undergoing cellular transformation after commencement of apoptosis through the blebbishield emergency program in a VEGF-VEGFR2-dependent manner. Development of therapeutics targeting the blebbishield emergency program would thus be important in cancer therapy. Specificity protein 1 (Sp1) orchestrates the transcription of both VEGF and VEGFR2; hence, Sp1 could act as a therapeutic target. Here, we demonstrate that CF3DODA-Me induced apoptosis, degraded Sp1, inhibited the expression of multiple drivers of the blebbishield emergency program such as VEGFR2, p70S6K, and N-Myc through act...
Source: Apoptosis - March 10, 2017 Category: Molecular Biology Source Type: research

Taurine ameliorated homocysteine-induced H9C2 cardiomyocyte apoptosis by modulating endoplasmic reticulum stress
This study aimed to evaluate the opposite effects of taurine on Hcy-induced cardiomyocyte apoptosis and their underlying mechanisms. Our results demonstrated that low-dose or short-term Hcy treatment increased the expression of glucose-regulated protein 78 (GRP78) and activated protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6), which in turn prevented apoptotic cell death. High-dose Hcy or prolonged Hcy treatment duration significantly up-regulated levels of C/EBP homologous protein (CHOP), cleaved caspase-12, p-c-JunN-terminal kinase (JNK), and then ...
Source: Apoptosis - February 21, 2017 Category: Molecular Biology Source Type: research

Exposure to chronic hyperglycemic conditions results in Ras-related C3 botulinum toxin substrate 1 (Rac1)-mediated activation of p53 and ATM kinase in pancreatic β-cells
In conclusion, these data indicate that sustained activation of Rac1-p38MAPK signaling axis leads to activation of p53 leading to β-cell dysfunction under the d uress of chronic hyperglycemic conditions. (Source: Apoptosis)
Source: Apoptosis - February 20, 2017 Category: Molecular Biology Source Type: research

Anandamide oxidative metabolism-induced endoplasmic reticulum stress and apoptosis
In this study, we aimed to disclose the mechanisms underlying the effects of AEA in human endometrial stromal cell fate, using a human-derived endometrial cell line (St-T1b). We found that AEA has an anti-proliferative activity through a direct effect on cell cycle progression by inducing G2/M arrest. Moreover, high levels of AEA increased COX-2 activity, triggering apoptotic cell death, with loss of mitochondrial membrane potential, induction of caspase -9 and -3/-7 activities, and cleavage of poly (ADP-ribose) polymerase (PARP). In addition, the involvement of intracellular reactive oxygen species (ROS) and endoplasmic r...
Source: Apoptosis - February 19, 2017 Category: Molecular Biology Source Type: research

Ursolic acid-mediated changes in glycolytic pathway promote cytotoxic autophagy and apoptosis in phenotypically different breast cancer cells
AbstractPlant-derived pentacyclic triterpenotids with multiple biological activities are considered as promising candidates for cancer therapy and prevention. However, their mechanisms of action are not fully understood. In the present study, we have analyzed the effects of low dose treatment (5 –20 µM) of ursolic acid (UA) and betulinic acid (BA) on breast cancer cells of different receptor status, namely MCF-7 (ER+, PR+/ −, HER2−), MDA-MB-231 (ER−, PR−, HER2−) and SK-BR-3 (ER−, PR−, HER2+). UA-mediated response was more potent than BA-mediated response. Triterpen...
Source: Apoptosis - February 16, 2017 Category: Molecular Biology Source Type: research

Remifentanil postconditioning ameliorates histone H3 acetylation modification in H9c2 cardiomyoblasts after hypoxia/reoxygenation via attenuating endoplasmic reticulum stress
In this study, an in vitro IRI model was established with H9c2 cardiomyoblasts to investigate the role of histone H3 acetylation and HDAC3 in RPC-induced attenuation of ERS-associated apoptosis. Briefly, H9c2 cardiomyoblasts were randomly subjected to hypoxia/reoxygenation with and without remifentanil administered at the onset of reoxygenation. Results showed that RPC increased cell viability and prevented cell apoptosis (evidenced by CCK-8 cell viability assays and flow cytometry), and these effects were accompanied by lower levels of expression of GRP78, CHOP, cleaved caspase-12, and cleaved caspase-3. RPC also mimicked...
Source: Apoptosis - February 15, 2017 Category: Molecular Biology Source Type: research

Heat shock protein 70 protects cardiomyocytes through suppressing SUMOylation and nucleus translocation of phosphorylated eukaryotic elongation factor 2 during myocardial ischemia and reperfusion
AbstractMyocardial ischemia and reperfusion (MIR) results in cardiomyocyte apoptosis with severe outcomes, which blocks cardiac tissue recovering from myocardial ischemia diseases. Heat shock protein 70 (HSP70) is one of protective molecule chaperones which could regulate the nucleus translocation of other proteins. In addition, eukaryotic elongation factor 2 (eEF2), which modulates protein translation process, is vital to the recovery of heart during MIR. However, the relationship between HSP70 and eEF2 and its effects on MIR are unclear. The expression and relationship between HSP70 and eEF2 is confirmed by western blot,...
Source: Apoptosis - February 14, 2017 Category: Molecular Biology Source Type: research

Apoptosis induced by a snake venom metalloproteinase from Bothrops alternatus venom in C2C12 muscle cells
In conclusion, our results suggest that the absence of appropriate extracellular matrix contacts triggers anoikis. Therefore, this is the first report that demonstrated the mechanism of programmed cell death triggered by baltergin, a PIII metalloprotease isolated fromBothrops alternatus venom, in a myoblast cell line. (Source: Apoptosis)
Source: Apoptosis - February 14, 2017 Category: Molecular Biology Source Type: research

Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival
AbstractImpaired apoptosis is one of the hallmarks of cancer. Caspase-3 and -8 are key regulators of the apoptotic response and have been shown to interact with the calpain family, a group of cysteine proteases, during tumorigenesis. The current study sought to investigate the prognostic potential of caspase-3 and -8 in breast cancer, as well as the prognostic value of combinatorial caspase and calpain expression. A large cohort (n  = 1902) of early stage invasive breast cancer patients was used to explore the expression of caspase-3 and -8. Protein expression was examined using standard immunohistochemistry ...
Source: Apoptosis - February 14, 2017 Category: Molecular Biology Source Type: research

Quercetin induces protective autophagy and apoptosis through ER stress via the p-STAT3/Bcl-2 axis in ovarian cancer
AbstractQuercetin (3,3 ′,4′,5,7-pentahydroxyflavone, Qu) is a promising cancer chemo-preventive agent for various cancers because it inhibits disease progression and promotes apoptotic cell death. In our previous study, we demonstrated that Qu could evoke ER stress to enhance drug cytotoxicity in ovarian cancer (OC). However, Qu-induced ER stress in OC is still poorly understood. Here, we demonstrated that Qu evoked ER stress to involve in mitochondria apoptosis pathway via the p-STAT3/Bcl-2 axis in OC cell lines and in primary OC cells. Unexpectedly, inhibition of ER stress did not reverse Qu-induced cell deat...
Source: Apoptosis - February 9, 2017 Category: Molecular Biology Source Type: research

Activation of Na + -K + -ATPase with DRm217 attenuates oxidative stress-induced myocardial cell injury via closing Na + -K + -ATPase/Src/Ros amplifier
AbstractReduced Na+-K+-ATPase activity has close relationship with cardiomyocyte death. Reactive oxygen species (ROS) also plays an important role in cardiac cell damage. It has been proved that Na+-K+-ATPase and ROS form a feed-forward amplifier. The aim of this study was to explore whether DRm217, a proved Na+/K+-ATPase ’s DR-region specific monoclonal antibody and direct activator, could disrupt Na+-K+-ATPase/ROS amplifier and protect cardiac cells from ROS-induced injury. We found that DRm217 protected myocardial cells against hydrogen peroxide (H2O2)-induced cardiac cell injury and mitochondrial dysfunction. DRm...
Source: Apoptosis - February 7, 2017 Category: Molecular Biology Source Type: research

Centchroman induces redox-dependent apoptosis and cell-cycle arrest in human endometrial cancer cells
This study focuses on the basis of antineoplasticity of CC by blocking the targets involved in the cell cycle, survival and apoptosis in endometrial cancer cells. Ishikawa Human Endometrial Cancer Cells were cultured under estrogen deprived medium, exposed to CC and analyzed for proliferation and apoptosis. Additionally, we also analyzed oxidative stress induced by CC. Cell viability studies confirmed the IC50 of CC in Ishikawa cells to be 20  µM after 48 h treatment. CC arrests the cells in G0/G1 phase through cyclin D1 and cyclin E mediated pathways. Phosphatidylserine externalization, nuclear morphology ...
Source: Apoptosis - February 6, 2017 Category: Molecular Biology Source Type: research

Propofol attenuates H 2 O 2 -induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes
AbstractPrevious studies have shown that propofol, an intravenous anesthetic commonly used in clinical practice, protects the myocardium from injury. Mitochondria- and endoplasmic reticulum (ER)-mediated oxidative stress and apoptosis are two important signaling pathways involved in myocardial injury and protection. The present study aimed to test the hypothesis that propofol could exert a cardio-protective effect via the above two pathways. Cultured neonatal rat cardiomyocytes were treated with culture medium (control group), H2O2 at 500  μM (H2O2 group), propofol at 50  μM (propofol group), and H2O2 plus ...
Source: Apoptosis - February 6, 2017 Category: Molecular Biology Source Type: research