Mycobacterium avium MAV2052 protein induces apoptosis in murine macrophage cells through Toll-like receptor 4
In this study, using multidimensional fractionation, we identified MAV2052 protein, which induced macrophage apoptosis in M. avium culture filtrates. The recombinant MAV2052 induced macrophage apoptosis in a caspase-dependent manner. The loss of mitochondrial transmembrane potential (ΔΨm), mitochondrial translocation of Bax, and release of cytochrome c from mitochondria were observed in macrophages treated with MAV2052. Further, reactive oxygen species (ROS) production was required for the apoptosis induced by MAV2052. In addition, ROS and mitogen-activated protein kinases were involved in MAV2052-mediated TNF-&a...
Source: Apoptosis - February 3, 2016 Category: Molecular Biology Source Type: research

Profilin potentiates chemotherapeutic agents mediated cell death via suppression of NF-κB and upregulation of p53
Abstract The molecular mechanism by which Profilin acts as a tumor suppressor is still unclear. Several chemotherapeutic agents, used till date either have unfavorable side effects or acquired resistance in tumor cells. Our findings show that Profilin enhances cell death mediated by several chemotherapeutic-agents. The activation of NF-κB and its dependent genes, mediated by paclitaxel and vinblastine, was completely inhibited in Profilin overexpressing cells. This inhibition was due to the Profilin mediated attenuation of IκBα degradation, thereby preventing p65 nuclear translocation and low NF-...
Source: Apoptosis - February 3, 2016 Category: Molecular Biology Source Type: research

GSIV serine/threonine kinase can induce apoptotic cell death via p53 and pro-apoptotic gene Bax upregulation in fish cells
In this study, we demonstrated that the Giant seaperch iridovirus (GSIV) genome encoded a serine/threonine kinase (ST kinase) protein, and induced apoptotic cell death via a p53-mediated Bax upregulation approach and a downregulation of Bcl-2 in fish cells. The ST kinase expression profile was identified through Western blot analyses, which indicated that expression started at day 1 h post-infection (PI), increased up to day 3, and then decreased by day 5 PI. This profile indicated the role of ST kinase expression during the early and middle phases of viral replication. We then cloned the ST kinase gene and tested its...
Source: Apoptosis - January 30, 2016 Category: Molecular Biology Source Type: research

Erratum to: Phosphocreatine protects against LPS-induced human umbilical vein endothelial cell apoptosis by regulating mitochondrial oxidative phosphorylation
(Source: Apoptosis)
Source: Apoptosis - January 29, 2016 Category: Molecular Biology Source Type: research

Knockdown of α-synuclein in cerebral cortex improves neural behavior associated with apoptotic inhibition and neurotrophin expression in spinal cord transected rats
Abstract Spinal cord injury (SCI) often causes severe functional impairment with poor recovery. The treatment, however, is far from satisfaction, and the mechanisms remain unclear. By using proteomics and western blot, we found spinal cord transection (SCT) resulted in a significant down-regulation of α-synuclein (SNCA) in the motor cortex of SCT rats at 3 days post-operation. In order to detect the role of SNCA, we used SNCA-ORF/shRNA lentivirus to upregulate or knockdown SNCA expression. In vivo, SNCA-shRNA lentivirus injection into the cerebral cortex motor area not only inhibited SNCA expression, bu...
Source: Apoptosis - January 28, 2016 Category: Molecular Biology Source Type: research

Inhibition of heme oxygenase-1 enhances the chemosensitivity of laryngeal squamous cell cancer Hep-2 cells to cisplatin
Abstract It has been previously reported that cisplatin is a well-known anticancer drug being used against a wide range of malignancies including head and neck, ovarian and non-small cell lung carcinoma, and demonstrated its anticancer activity by reacting with DNA or changing cell structure, immune response, reactive oxygen species level (ROS). In this research we proved that cisplatin induced cell injuries and heme oxygenase-1 (HO-1) expression in laryngeal squamous cell cancer Hep-2 cells through ROS generation. The induction of HO-1 clearly protected Hep-2 cells from cisplatin-induced cell death and ROS reacti...
Source: Apoptosis - January 22, 2016 Category: Molecular Biology Source Type: research

Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress
This study seeks to determine if caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress in myoblast and its underlying mechanism. Apoptosis was assessed by Hochest staining, DAPI staining and annexin V binding and PI staining. ER chaperones, such as GRP78, CHOP and caspase-12, were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Furthermore, caspase-12 inhibitor was used to value the mechanism of the caspase-12 pathway. Apoptosis of myoblast, which is subjected to cyclic stretch, was observed in a time-dependent manner. We found that GRP78 mRNA and...
Source: Apoptosis - January 22, 2016 Category: Molecular Biology Source Type: research

Necroptosis: a potential, promising target and switch in acute pancreatitis
This article reviewed the progress of necroptosis in AP to provide a reference for deeply understanding the pathogenic mechanisms of AP and identifying new therapeutic targets. (Source: Apoptosis)
Source: Apoptosis - January 14, 2016 Category: Molecular Biology Source Type: research

Enhanced autophagy reveals vulnerability of P-gp mediated epirubicin resistance in triple negative breast cancer cells
Abstract Epirubicin (EPI) is widely used for triple negative breast cancer (TNBC), but a substantial number of patients develop EPI resistance that is associated with poor outcome. The underlying mechanism for EPI resistance remains poorly understood. We have developed and characterized an EPI-resistant (EPI-R) cell line from parental MDA-MB-231 cells. These EPI-R cells reached stable growth in the medium containing 8 μg/ml of EPI. They overexpressed P-glycoprotein (P-gp) and contained numerous autophagic vacuoles. The suppression of P-gp overexpression and/or autophagy restored the sensitivity of these EP...
Source: Apoptosis - January 14, 2016 Category: Molecular Biology Source Type: research

Human islet cells are killed by BID-independent mechanisms in response to FAS ligand
Abstract Cell death via FAS/CD95 can occur either by activation of caspases alone (extrinsic) or by activation of mitochondrial death signalling (intrinsic) depending on the cell type. The BH3-only protein BID is activated in the BCL-2-regulated or mitochondrial apoptosis pathway and acts as a switch between the extrinsic and intrinsic cell death pathways. We have previously demonstrated that islets from BID-deficient mice are protected from FAS ligand-mediated apoptosis in vitro. However, it is not yet known if BID plays a similar role in human beta cell death. We therefore aimed to test the role of BID in human ...
Source: Apoptosis - January 12, 2016 Category: Molecular Biology Source Type: research

Membrane-bound heat shock proteins facilitate the uptake of dying cells and cross-presentation of cellular antigen
Abstract Heat shock proteins (HSPs) were originally identified as stress-responsive proteins and serve as molecular chaperones in different intracellular compartments. Translocation of HSPs to the cell surface and release of HSPs into the extracellular space have been observed during the apoptotic process and in response to a variety of cellular stress. Here, we report that UV irradiation and cisplatin treatment rapidly induce the expression of membrane-bound Hsp60, Hsp70, and Hsp90 upstream the phosphatidylserine exposure. Membrane-bound Hsp60, Hsp70 and Hsp90 could promote the release of IL-6 and IL-1β...
Source: Apoptosis - January 1, 2016 Category: Molecular Biology Source Type: research

Advanced oxidation protein products induce chondrocyte apoptosis via receptor for advanced glycation end products-mediated, redox-dependent intrinsic apoptosis pathway
Abstract Pro-inflammatory cytokine-induced chondrocyte apoptosis is a primary cause of cartilage destruction in the progression of rheumatoid arthritis (RA). Advanced oxidation protein products (AOPPs), a novel pro-inflammatory mediator, have been confirmed to accumulate in patients with RA. However, the effect of AOPPs accumulation on chondrocyte apoptosis and the associated cellular mechanisms remains unclear. The present study demonstrated that the plasma formation of AOPPs was enhanced in RA rats compared with normal. Then, chondrocyte were treated with AOPPs-modified rat serum albumin (AOPPs-RSA) in vitro. E...
Source: Apoptosis - January 1, 2016 Category: Molecular Biology Source Type: research

Bcl-2 silencing attenuates hypoxia-induced apoptosis resistance in pulmonary microvascular endothelial cells
This study therefore reveals critical insight into potential therapeutic targets for treating PAH. (Source: Apoptosis)
Source: Apoptosis - January 1, 2016 Category: Molecular Biology Source Type: research

Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis
Abstract Apoptosis is a normally biological phenomenon in various organisms, involving complexly molecular mechanisms with a series of signaling processes. Notch signaling is found evolutionarily conserved in many species, playing a critical role in embryonic development, normal tissue homeostasis, angiogenesis and immunoregulation. The focus of this review is on currently novel advances about roles of CSL-dependent and independent Notch signaling pathways in cell apoptosis. The CSL can bind Notch intracellular domain (NIC) to act as a switch in mediating transcriptional activation or inactivation of th...
Source: Apoptosis - January 1, 2016 Category: Molecular Biology Source Type: research

Krabbe disease: involvement of connexin43 in the apoptotic effects of sphingolipid psychosine on mouse oligodendrocyte precursors
In this study, some apoptotic markers such as apoptotic index (AI), DNA fragmentation, caspase-3, PTEN, Bad, and PI3K were determined in oligodendrocyte precursors from wild type or twitcher mice untreated or treated with psychosine. Twitcher is a natural mouse model of Krabbe disease containing a premature stop codon (W339X) in the β-galactosylceramidase gene. Moreover, a possible involvement of connexin (Cx)43 in cell death of oligodendrocyte precursors induced by psychosine was investigated with the final aim to provide a contribution to the knowledge of the molecular mechanisms and pathophysiological events that o...
Source: Apoptosis - January 1, 2016 Category: Molecular Biology Source Type: research

Beta1 integrin inhibits apoptosis induced by cyclic stretch in annulus fibrosus cells via ERK1/2 MAPK pathway
Abstract Low back pain is associated with intervertebral disc degeneration (IVDD) due to cellular loss through apoptosis. Mechanical factors play an important role in maintaining the survival of the annulus fibrosus (AF) cells and the deposition of extracellular matrix. However, the mechanisms that excessive mechanical forces lead to AF cell apoptosis are not clear. The present study was to look for how AF cells sense mechanical changes. In vivo experiments, the involvement of mechanoreceptors in apoptosis was examined by RT-PCR and/or immunoblotting in the lumbar spine of rats subjected to unbalanced dynamic and...
Source: Apoptosis - January 1, 2016 Category: Molecular Biology Source Type: research

Knockdown of HIF-1α and IL-8 induced apoptosis of hepatocellular carcinoma triggers apoptosis of vascular endothelial cells
This study aimed to evaluate whether knockdown of HIF-1α and IL-8 induced apoptosis of the hepatocellular carcinoma (HCC) and endothelial cell lines. HCC cell lines were infected with adenovirus-expressing shRNA for HIF-1α and IL-8 and maintained under hypoxic conditions (1 % O2, 24 h). The expression levels of HIF-1α and both apoptotic and growth factors were examined by real-time quantitative PCR and western blot. We also investigated apoptosis by TUNEL assay (FACS and Immunofluorescence) and measured the concentration of cytochrome C. Inhibition of HIF-1α and IL-8 up-regulated the expre...
Source: Apoptosis - January 1, 2016 Category: Molecular Biology Source Type: research

CD147 is increased in HCC cells under starvation and reduces cell death through upregulating p-mTOR in vitro
In this study, using an Earle’s Balanced Salt Solution medium culture model that mimics nutrient deprivation induced by TACE, we investigated the regulation of CD147 expression on HCC cells under starvation conditions and its functional effects on HCC cell death. During early stages of starvation, the expression of CD147 was considerably upregulated in SMMC7721, HepG2 and HCC9204 hepatoma cell lines at the protein levels. Downregulation of CD147 by specific small interfering RNA (siRNA) significantly promoted starvation-induced cell death. In addition, CD147 siRNA-transfected SMMC7721 cells demonstrated significantly...
Source: Apoptosis - January 1, 2016 Category: Molecular Biology Source Type: research

PEDF and 34-mer inhibit angiogenesis in the heart by inducing tip cells apoptosis via up-regulating PPAR-γ to increase surface FasL
Abstract Pigment epithelial-derived factor (PEDF) is a potent anti-angiogenic factor whose effects are partially mediated through the induction of endothelial cell apoptosis. However, the underlying mechanism for PEDF and the functional PEDF peptides 34-mer and 44-mer to inhibit angiogenesis in the heart has not been fully established. In the present study, by constructing adult Sprague–Dawley rat models of acute myocardial infarction (AMI) and in vitro myocardial angiogenesis, we showed that PEDF and 34-mer markedly inhibits angiogenesis by selectively inducing tip cells apoptosis rather than quiescent cel...
Source: Apoptosis - January 1, 2016 Category: Molecular Biology Source Type: research

Synergistic effect of apoptosis and necroptosis inhibitors in cisplatin-induced nephrotoxicity
In conclusion, our study has a significant potential to show in vitro and in vivo protection obtained by necrostatin-1. Therefore, our results suggest that necroptosis may be an important mechanism of cell death after kidney injury. (Source: Apoptosis)
Source: Apoptosis - January 1, 2016 Category: Molecular Biology Source Type: research

PPM1D exerts its oncogenic properties in human pancreatic cancer through multiple mechanisms
In this study, we determined PPM1D expression in human PC tissues and cell lines and their irrespective noncancerous controls. We subsequently investigated the functional role of PPM1D in the migration, invasion, and apoptosis of MIA PaCa-2 and PANC-1 PC cells in vitro and explored the signaling pathways involved. Furthermore, we examined the role of PPM1D in PC tumorigenesis in vivo. Our results showed that PPM1D is overexpressed in human PC tissues and cell lines and significantly correlated with tumor growth and metastasis. PPM1D promotes PC cell migration and invasion via potentiation of the Wnt/β-catenin pathway ...
Source: Apoptosis - December 29, 2015 Category: Molecular Biology Source Type: research

Drosophila MOF regulates DIAP1 and induces apoptosis in a JNK dependent pathway
Abstract Histone modulations have been implicated in various cellular and developmental processes where in Drosophila Mof is involved in acetylation of H4K16. Reduction in the size of larval imaginal discs is observed in the null mutants of mof with increased apoptosis. Deficiency involving Hid, Reaper and Grim [H99] alleviated mof RNAi induced apoptosis in the eye discs. mof RNAi induced apoptosis leads to activation of caspases which is suppressed by over expression of caspase inhibitors like P35 and Diap1clearly depicting the role of casp...
Source: Apoptosis - December 28, 2015 Category: Molecular Biology Source Type: research

Phosphocreatine protects against LPS-induced human umbilical vein endothelial cell apoptosis by regulating mitochondrial oxidative phosphorylation
Abstract Phosphocreatine (PCr) is an exogenous energy substance, which provides phosphate groups for adenosine triphosphate (ATP) cycle and promotes energy metabolism in cells. However, it is still unclear whether PCr has influenced on mitochondrial energy metabolism as well as oxidative phosphorylation (OXPHO) in previous studies. Therefore, the aim of the present study was to investigate the regulation of PCr on lipopolsaccharide (LPS)-induced human umbilical vein endothelial cells (HUVECs) and mitochondrial OXPHO pathway. PCr protected HUVECs against LPS-induced apoptosis by suppressing the mitochondrial pe...
Source: Apoptosis - December 26, 2015 Category: Molecular Biology Source Type: research

Stem cell death and survival in heart regeneration and repair
Abstract Cardiovascular diseases are major causes of mortality and morbidity. Cardiomyocyte apoptosis disrupts cardiac function and leads to cardiac decompensation and terminal heart failure. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Stem cells displa...
Source: Apoptosis - December 19, 2015 Category: Molecular Biology Source Type: research

Apoptosis in Drosophila : which role for mitochondria?
Abstract It is now well established that the mitochondrion is a central regulator of mammalian cell apoptosis. However, the importance of this organelle in non-mammalian apoptosis has long been regarded as minor, mainly because of the absence of a crucial role for cytochrome c in caspase activation. Recent results indicate that the control of caspase activation and cell death in Drosophila occurs at the mitochondrial level. Numerous proteins, including RHG proteins and proteins of the Bcl-2 family that are key regulators of Drosophila apoptosis, constitutively or transiently localize in mitochondria. These pr...
Source: Apoptosis - December 17, 2015 Category: Molecular Biology Source Type: research

Survivin silencing and TRAIL expression using oncolytic adenovirus increase anti-tumorigenic activity in gemcitabine-resistant pancreatic cancer cells
In this study, we demonstrated that survivin downregulation with TRAIL expression greatly enhanced the cytotoxic death of pancreatic cancer cells after gemcitabine treatment. Using real-time RT-PCR, we analyzed five survivin shRNAs to identify the best target sequence for suppression of human survivin, with the goal of treating gemcitabine-resistant pancreatic cancer cells. Survivin shRNA 5, corresponding to target 5, showed the greatest reduction in survivin mRNA levels. Furthermore, combined treatment with survivin shRNA-expressing adenovirus with gemcitabine plus TRAIL decreased uncleaved PARP and increased consequent P...
Source: Apoptosis - December 16, 2015 Category: Molecular Biology Source Type: research

Dihydropyridines’ metabolites-induced early apoptosis after myocardial infarction in rats; new outlook on preclinical study with M-2 and M-3
Abstract Our previous studies established cardio-protective effects of furnidipine and its active metabolites called M-2 and M-3. The aim of current research was to compare the effects of single oral pretreatment with 20 mg kg−1 of M-2 and M-3 on mortality, different forms of arrhythmias, blood pressures parameters and ST-segment changes during occlusion (for 90 min) and reperfusion in the model of myocardial infarction in rats evoked by left anterior descending coronary artery occlusion. Additionally, the development of programmed cell death and biochemical parameters in blood serum were stud...
Source: Apoptosis - December 14, 2015 Category: Molecular Biology Source Type: research

Depletion of histone N-terminal-acetyltransferase Naa40 induces p53-independent apoptosis in colorectal cancer cells via the mitochondrial pathway
Abstract Protein N-terminal acetylation is an abundant post-translational modification in eukaryotes implicated in various fundamental cellular and biochemical processes. This modification is catalysed by evolutionarily conserved N-terminal acetyltransferases (NATs) whose deregulation has been linked to cancer development and thus, are emerging as useful diagnostic and therapeutic targets. Naa40 is a highly selective NAT that acetylates the amino-termini of histones H4 and H2A and acts as a sensor of cell growth in yeast. In the present study, we examine the role of Naa40 in cancer cell survival. We demonstrat...
Source: Apoptosis - December 14, 2015 Category: Molecular Biology Source Type: research

Thyroid hormones improve cardiac function and decrease expression of pro-apoptotic proteins in the heart of rats 14 days after infarction
Abstract Apoptosis is a key process associated with pathological cardiac remodelling in early-phase post-myocardial infarction. In this context, several studies have demonstrated an anti-apoptotic effect of thyroid hormones (TH). The aim of this study was to evaluate the effects of TH on the expression of proteins associated with the apoptotic process 14 days after infarction. Male Wistar rats (300–350 g) (n = 8/group) were divided into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT) and infarcted + TH (AMIT). For 12 days, the animal...
Source: Apoptosis - December 12, 2015 Category: Molecular Biology Source Type: research

Functional characterization of Mammary Gland Protein-40, a chitinase-like glycoprotein expressed during mammary gland apoptosis
Abstract MGP-40 is a chitinase-like protein which is over expressed during mammary gland involution. However, its physiological function in the mammary gland is poorly understood. In the present investigation, we have reported the functional significance of buffalo specific MGP-40 in the mammary gland by using an in vitro model of the buffalo mammary epithelial cell (BuMEC) line. MGP-40 was highly up regulated in BuMECs in serum starved condition as well as after treatment with prolactin suggesting its role in the stress response. Subsequently, to study the effect of MGP-40 on BuMECs, the cells were transfected wi...
Source: Apoptosis - December 10, 2015 Category: Molecular Biology Source Type: research

SOX6 and PDCD4 enhance cardiomyocyte apoptosis through LPS-induced miR-499 inhibition
In this study, we attempted to explore the mechanisms involved in LPS-induced cardiomyocyte apoptosis. We found that LPS stimulation inhibited microRNA (miR)-499 expression and thereby upregulated the expression of SOX6 and PDCD4 in neonatal rat cardiomyocytes. We demonstrate that SOX6 and PDCD4 are target genes of miR-499, and they enhance LPS-induced cardiomyocyte apoptosis by activating the BCL-2 family pathway. The apoptosis process enhanced by overexpression of SOX6 or PDCD4, was rescued by the cardiac-abundant miR-499. Overexpression of miR-499 protected the cardiomyocytes against LPS-induced apoptosis. In brief, our...
Source: Apoptosis - December 10, 2015 Category: Molecular Biology Source Type: research

JA, a new type of polyunsaturated fatty acid isolated from Juglans mandshurica Maxim, limits the survival and induces apoptosis of heptocarcinoma cells
In this study, we studied anti-tumor activity of JA on several human cancer cell lines. Results showed that JA is cytotoxic to HepG2, MDA-MB-231, SGC-7901, A549 and Huh7 cells at a concentration exerting minimal toxic effects on L02 cells. The selective toxicity of JA was better than other classical anti-cancer drugs. Further investigation indicated that JA could induce cell apoptosis, characterized by chromatin condensation, DNA fragmentation and activation of the apoptosis-associated proteins such as Caspase-3 and PARP-1. Moreover, we investigated the cellular apoptosis pathway involved in the apoptosis process in HepG2 ...
Source: Apoptosis - November 30, 2015 Category: Molecular Biology Source Type: research

Hepatoma derived growth factor (HDGF) dynamics in ovarian cancer cells
In this study, we focused on the circumstances under which HDGF is released by cells and the functional relevance of extracellular HDGF in the context of ovarian cancer. Immunofluorescence imaging showed nuclear localization of HDGF in ovarian cells, but unlike what is reported for other cell types, HDGF was minimally secreted into the media. However, HDGF was passively released by necrotic and late apoptotic cells. Extracellular HDGF was functionally relevant as it stimulated phosphorylation of ERK 1/2 and P38 in both non-cancer and ovarian cancer cells, and enhanced cellular migration. Overall, our study uncovers a novel...
Source: Apoptosis - November 26, 2015 Category: Molecular Biology Source Type: research

Anti-tumor activities of luteolin and silibinin in glioblastoma cells: overexpression of miR-7-1-3p augmented luteolin and silibinin to inhibit autophagy and induce apoptosis in glioblastoma in vivo
In conclusion, our results clearly demonstrated that overexpression of miR-7-1-3p augmented the anti-tumor activities of LUT and SIL to inhibit autophagy and induce apoptosis for controlling growth of different human glioblastomas in vivo. (Source: Apoptosis)
Source: Apoptosis - November 16, 2015 Category: Molecular Biology Source Type: research

Human lactoferrin triggers a mitochondrial- and caspase-dependent regulated cell death in Saccharomyces cerevisiae
This study provides new insights into a detailed understanding at the molecular level of hLf-induced apoptosis, which may allow the design of new strategies to overcome the emergence of resistance of clinically relevant fungi to conventional antifungals. (Source: Apoptosis)
Source: Apoptosis - November 14, 2015 Category: Molecular Biology Source Type: research

Caspase-mediated cleavage of Beclin1 inhibits autophagy and promotes apoptosis induced by S1 in human ovarian cancer SKOV3 cells
Abstract S1, a novel BH3 mimetic, can induce apoptosis dependent on Bax/Bak through inhibition of Bcl-2 in various tumors. S1 also induces autophagy through interrupting the interaction of Bcl-2 and Beclin1. Our results showed that S1 induces apoptosis in human ovarian cancer SKOV3 cells in a time- and dose-dependent manner. Autophagy precedes apoptosis, in SKOV3 cells treated with S1 (6 μmol/L), autophagy reached the maximum peak at 12 h after treatment and decreased to 24 h. In SKOV3 cells treated with different concentrations of S1 for 24 h, the highest level of autophagy was observed wit...
Source: Apoptosis - November 14, 2015 Category: Molecular Biology Source Type: research

Hemagglutinin protease secreted by V. cholerae induced apoptosis in breast cancer cells by ROS mediated intrinsic pathway and regresses tumor growth in mice model
In this study we have shown antitumor activity of hemagglutinin protease (HAP) secreted by Vibrio cholerae. One µg of HAP showed potent antitumor activity when injected into Ehrlich ascites carcinoma (EAC) tumors in Swiss albino mice. Weekly administration of this dose is able to significantly diminish a large tumor volume within 3 weeks and increases the survival rates of cancerous mice. HAP showed apoptotic activity on EAC and other malignant cells. Increased level of pro-apoptotic p53 with increased ratio of pro-apoptotic Bax to anti-apoptotic Bcl-2 signify that HAP induced apoptogenic signals lead to death o...
Source: Apoptosis - November 11, 2015 Category: Molecular Biology Source Type: research

Does melatonin influence the apoptosis in rat uterus of animals exposed to continuous light?
Abstract Melatonin has been described as a protective agent against cell death and oxidative stress in different tissues, including in the reproductive system. However, the information on the action of this hormone in rat uterine apoptosis is low. Our objective was to evaluate the effects of melatonin on mechanisms of cell death in uterus of rats exposed to continuous light stress. Twenty adult Wistar rats were divided into two groups: GContr (vehicle control) and GExp which were treated with melatonin (0.4 mg/mL), both were exposed to continuous light for 90 days. The uterus was removed and processed fo...
Source: Apoptosis - November 5, 2015 Category: Molecular Biology Source Type: research

Chemotherapeutic agent CPT-11 eliminates peritoneal resident macrophages by inducing apoptosis
In this study, we evaluated the cytotoxic effects of CPT-11 on mouse peritoneal resident macrophages. CPT-11 was administered intraperitoneally to mice and their peritoneal exudate cells were isolated for evaluation. CPT-11 treatment strikingly decreased the ratio of F4/80hiMHCIIlow large peritoneal macrophages (LPMs), which are regarded as prenatally-originated peritoneal resident macrophages. Consistent with this, the transcription factor GATA6 specifically expressed in LPMs was barely detectable in the macrophages from CPT-11-treated mice, indicative of elimination of LPMs. Such elimination of LPMs was at least partly d...
Source: Apoptosis - November 3, 2015 Category: Molecular Biology Source Type: research

Phosphocreatine protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by modulating the PI3K/Akt/eNOS pathway
In conclusion, our data show that the inhibition of oxLDL-induced endothelial apoptosis by PCr is due, at least in part to its anti-oxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway. (Source: Apoptosis)
Source: Apoptosis - October 12, 2015 Category: Molecular Biology Source Type: research

SZC017, a novel oleanolic acid derivative, induces apoptosis and autophagy in human breast cancer cells
In this study, we elucidated the anticancer effect of SZC017, a novel OA derivative and identified the mechanisms by which SZC017 induces MCF-7 cell death. We found that SZC017 effectively decreased the cell viability of these breast cancer cells, but was less toxic to MCF10A mammary epithelial cells. Mechanisms underlying the inhibition of cell viability are apoptosis, autophagy induction, and G0/G1 phase arrest. SZC017 treatment suppressed the levels of Akt, phosphorylated-Akt (p-Akt), p-IκBα, total p65, and total p-p65, in addition to p-p65 in both the cytoplasm and nucleus. Furthermore, the inhibition of p6...
Source: Apoptosis - October 12, 2015 Category: Molecular Biology Source Type: research

SYK is a target of lymphocyte-derived microparticles in the induction of apoptosis of human retinoblastoma cells
This report demonstrated that LMPs have potent pro-apoptotic properties on human Rb cells, which was associated with a strong reduction of SYK expression. Perturbing SYK activity in Rb cells induced cell apoptosis and upregulated expression of p53 and p21. Interestingly, inhibition of p53 or knockdown of p21, abolished LMP-induced caspase-3 activity and cell death. Blocking oxidized phospholipid-rich LMPs with a specific antibody significantly prevented LMP-induced Rb apoptosis and reversed the expression patterns of SYK, p53, p21. In summary, our results suggest that LMPs are important pro-apoptotic regulators for Rb cell...
Source: Apoptosis - October 12, 2015 Category: Molecular Biology Source Type: research

AMBRA1 and SQSTM1 expression pattern in prostate cancer
Abstract Prostate cancer is among the most commonly diagnosed male diseases and a leading cause of cancer mortality in men. There is emerging evidence that autophagy plays an important role in malignant cell survival and offers protection from the anti-cancer drugs in prostate cancer cells. AMBRA1 and the autophagic protein sequestosome-1 (SQSTM1; p62) expression were evaluated by immunohistochemistry and western blot on tissue samples from both benign and malignant prostatic lesions. The data reported in this pilot study demonstrated an increased expression of AMBRA1 and SQSTM1, which were also associated with a...
Source: Apoptosis - October 12, 2015 Category: Molecular Biology Source Type: research

Erratum to: Flt3 receptor inhibition reduces constitutive NF κ B activation in high-risk myelodysplastic syndrome and acute myeloid leukemia
(Source: Apoptosis)
Source: Apoptosis - October 12, 2015 Category: Molecular Biology Source Type: research

Low zinc environment induces stress signaling, senescence and mixed cell death modalities in colon cancer cells
In conclusion, presented results demonstrate variability of responses to chronic zinc depletion in colon cancer as modeled in vitro. (Source: Apoptosis)
Source: Apoptosis - October 7, 2015 Category: Molecular Biology Source Type: research

Apoptotic and autophagic cell death induced by glucolaxogenin in cervical cancer cells
Abstract The antiproliferative and cytotoxic activity of glucolaxogenin and its ability to induce apoptosis and autophagy in cervical cancer cells are reported. We ascertained that glucolaxogenin exerts an inhibitory effect on the proliferation of HeLa, CaSki and ViBo cells in a dose-dependent manner. Analysis of DNA distribution in the cell-cycle phase of tumor cells treated with glucolaxogenin suggests that the anti-proliferative activity of this steroid is not always dependent on the cell cycle. Cytotoxic activity was evaluated by detection of the lactate dehydrogenase enzyme in supernatants from tumor cell...
Source: Apoptosis - October 5, 2015 Category: Molecular Biology Source Type: research

A novel dual EGFR/HER2 inhibitor KU004 induces cell cycle arrest and apoptosis in HER2-overexpressing cancer cells
In this study, we investigated the anticancer effect of KU004, a novel dual EGFR and HER2 inhibitor in vitro and in vivo. In vitro, KU004 preferentially inhibited the growth of HER2-overexpressing breast and gastric cell lines and HER2 expression level significantly correlated with response to KU004. It blocked activation of EGFR, HER2 and downstream Akt and Erk and induced G0/G1 arrest which was associated with downregulation of p53, p21, cyclin D1 and CDK4 along with increase of p27 and dephosphorylation of pRb. Apoptosis occurred in a caspase-dependent manner mainly via the extrinsic apoptotic pathway after KU004 treatm...
Source: Apoptosis - October 5, 2015 Category: Molecular Biology Source Type: research

Investigation of the mechanism and apoptotic pathway induced by 4β cinnamido linked podophyllotoxins against human lung cancer cells A549
Abstract Apoptosis is essential for normal development and the maintenance of homeostasis. It plays a necessary role to protect against carcinogenesis by eliminating damaged cells. Many studies have demonstrated that the dysregulation of apoptosis results in cancer and this provides an approach to develop therapeutic agents via inducing apoptosis. In our previous studies 4β-cinnamido linked podophyllotoxin conjugates were synthesized and evaluated for their cytotoxic activity in a panel of five human cancer cell lines and the new molecules like 17a and 17f were considered as potential leads. The cytotoxic ac...
Source: Apoptosis - September 19, 2015 Category: Molecular Biology Source Type: research

The acylphloroglucinols hyperforin and myrtucommulone A cause mitochondrial dysfunctions in leukemic cells by direct interference with mitochondria
Abstract The acylphloroglucinols hyperforin (Hypf) and myrtucommulone A (MC A) induce death of cancer cells by triggering the intrinsic/mitochondrial pathway of apoptosis, accompanied by a loss of the mitochondrial membrane potential and release of cytochrome c. However, the upstream targets and mechanisms leading to these mitochondrial events in cancer cells remain elusive. Here we show that Hypf and MC A directly act on mitochondria derived from human leukemic HL-60 cells and thus, disrupt mitochondrial functions. In isolated mitochondria, Hypf and MC A efficiently impaired mitochondrial viability (EC50 =&n...
Source: Apoptosis - September 19, 2015 Category: Molecular Biology Source Type: research

Apoptosis transcriptional mechanism of feline infectious peritonitis virus infected cells
This study is focused on apoptosis and transcriptional profiling of FIPV-infected cells following in vitro infection of CRFK cells with FIPV 79-1146 WSU. Flow cytometry was used to determine mode of cell death in first 42 h post infection (hpi). FIPV infected cells underwent early apoptosis at 9 hpi (p 
Source: Apoptosis - September 19, 2015 Category: Molecular Biology Source Type: research