Prodigiosin stimulates endoplasmic reticulum stress and induces autophagic cell death in glioblastoma cells
This study investigated the cell death mechanism of prodigiosin in glioblastoma. Glioblastoma multiforme (GBM) is an aggressive primary cancer of the central nervous system. Despite treatment, or standard therapy, the median survival of glioblastoma patients is about 14.6 month. The results of the present study clearly showed that prodigiosin significantly reduced the cell viability and neurosphere formation ability of U87MG and GBM8401 human glioblastoma cell lines. Moreover, prodigiosin with fluorescence signals was detected in the endoplasmic reticulum and found to induce excessive levels of autophagy. These findings we...
Source: Apoptosis - May 2, 2018 Category: Molecular Biology Source Type: research

Critical contribution of RIPK1 mediated mitochondrial dysfunction and oxidative stress to compression-induced rat nucleus pulposus cells necroptosis and apoptosis
AbstractThe aim of this study was to investigate whether RIPK1 mediated mitochondrial dysfunction and oxidative stress contributed to compression-induced nucleus pulposus (NP) cells necroptosis and apoptosis, together with the interplay relationship between necroptosis and apoptosis in vitro. Rat NP cells underwent various periods of 1.0  MPa compression. To determine whether compression affected mitochondrial function, we evaluated the mitochondrial membrane potential, mitochondrial permeability transition pore (mPTP), mitochondrial ultrastructure and ATP content. Oxidative stress-related indicators reactive oxygen s...
Source: Apoptosis - April 28, 2018 Category: Molecular Biology Source Type: research

Feasibility study of stain-free classification of cell apoptosis based on diffraction imaging flow cytometry and supervised machine learning techniques
This study was to explore the feasibility of prediction and classification of cells in different stages of apoptosis with a stain-free method based on diffraction images and supervised machine learning. Apoptosis was induced in human chronic myelogenous leukemia K562 cells bycis-platinum (DDP). A newly developed technique of polarization diffraction imaging flow cytometry (p-DIFC) was performed to acquire diffraction images of the cells in three different statuses (viable, early apoptotic and late apoptotic/necrotic) after cell separation through fluorescence activated cell sorting with Annexin V-PE and SYTOX ® Green d...
Source: Apoptosis - April 16, 2018 Category: Molecular Biology Source Type: research

Long noncoding RNAs in the mTOR signaling network: biomarkers and therapeutic targets
AbstractAs an evolutionarily conserved serine/threonine kinase of the phosphoinositide 3-kinase (PI3K) related kinase family, the mechanistic/mammalian target of rapamycin (mTOR) plays vital roles in the PI3K/AKT/mTOR pathway, participating in different cellular processes including cell survival, metabolism and proliferation. Aberrant activity of this signaling pathway may lead to oncogenesis. Over the last two decades, great progress has been made in the understanding of mTOR activation and how its response is counteracted for maintaining tissue homeostasis. Besides regulatory proteins and microRNAs, long noncoding RNA (l...
Source: Apoptosis - March 19, 2018 Category: Molecular Biology Source Type: research

Correction to: Licarin A induces cell death by activation of autophagy and apoptosis in non-small cell lung cancer cells
The original version of this article unfortunately contained a mistake. (Source: Apoptosis)
Source: Apoptosis - March 15, 2018 Category: Molecular Biology Source Type: research

Dysregulated genes and miRNAs in the apoptosis pathway in colorectal cancer patients
We examined 133 genes within these pathways to identify whether they are expressed differently in colorectal carcinoma (CRC) and normal tissue (N  = 217) and if they are associated with similar differential miRNA expression. Gene expression data (RNA-Seq) and miRNA expression data (Agilent Human miRNA Microarray V19.0) were generated. We focused on dysregulated genes with a fold change (FC) of>  1.50 or
Source: Apoptosis - March 7, 2018 Category: Molecular Biology Source Type: research

Role of p62 in the regulation of cell death induction
Abstractp62 is a multifunctional adaptor protein implicated in various cellular processes. It has been found to regulate selective autophagy, cell survival, cell death, oxidative stress, DNA repair and inflammation, and to play a role in a number of diseases, such as tumourigenesis, Paget ’s disease of bone, neurodegenerative disease, diabetes, and obesity. Cell death induction is an important cellular process. The dysregulation of cell death induction is involved in the pathogenesis of various diseases, such as cancer, neurodegeneration diseases, and diabetes. In this review, we d iscuss the functional role of p62 i...
Source: Apoptosis - February 26, 2018 Category: Molecular Biology Source Type: research

Epirubicin induces apoptosis in osteoblasts through death-receptor and mitochondrial pathways
AbstractEpirubicin is an anthracycline and is widely used in tumor treatment, but has toxic and undesirable side effects on wide range of cells and hematopoietic stem cells (HSC). Osteoblasts play important roles in bone development and in supporting HSC differentiation and maturation. It remains unknown whether epirubicin-induced bone loss and hematological toxicity are associated with its effect on osteoblasts. In primary osteoblast cell cultures, epirubicin inhibited cell growth and decreased mineralization. Moreover, epirubicin arrested osteoblasts in the G2/M phase, and this arrest was followed by apoptosis in which b...
Source: Apoptosis - February 21, 2018 Category: Molecular Biology Source Type: research

Licarin A induces cell death by activation of autophagy and apoptosis in non-small cell lung cancer cells
This study investigated the anti-proliferative effect of Licarin A (LCA) fromMyristica fragrans in non-small cell lung cancer cell lines —A549, NCI-H23, NCI-H520 and NCI-H460. LCA inhibited proliferation of all the four cell lines in a dose and time dependent manner with minimum IC50 of 20.03 ± 3.12, 22.19 ± 1.37 µM in NCI-H23 and A549 cells respectively. Hence NCI-H23 and A549 cells were used to assess the ability LCA to induce autophagy and apoptosis. LCA treatment caused G1 arrest, increase in Beclin 1, LC3II levels and degradation of p62 indicating activation o...
Source: Apoptosis - February 21, 2018 Category: Molecular Biology Source Type: research

Effect of phosphorylation and single nucleotide polymorphisms on caspase substrates processing
In this study, we predicted how phosphorylation and SNPs affect known human caspas e proteolytic events collected in the CASBAH and Degrabase databases by applying Random Forest caspases’ substrates prediction method, as implemented in the CaspDB, and the molecular dynamics free energy simulations approach. Our analysis confirms several experimental observations. Phosphorylation could have both positive or negative regulatory effects depending on its position with respect to the caspase cleavage site. For instance, we demonstrate that phosphorylation at P1′ is the most detrimental for proteolytic efficiency of ...
Source: Apoptosis - February 16, 2018 Category: Molecular Biology Source Type: research

Hypertonicity primes malignant melanoma cells for apoptosis
AbstractThe tumor environment critically influences responsiveness of cancer cells to chemotherapies, most of which activate the mitochondria-regulated (intrinsic) apoptotic cascade to kill malignant cells. Especially skin tumors encounter an environment with remarkable biophysical properties. Cutaneous accumulation of Na+ locally establishes osmotic pressure gradients in vivo (hypertonicity or hyperosmotic stress), but whether cutaneous hypertonicity is a factor that modulates the responsiveness of skin cancers to therapeutic apoptosis-induction has thus far not been investigated. Here, we show that hyperosmotic stress lo...
Source: Apoptosis - February 13, 2018 Category: Molecular Biology Source Type: research

Plagioneurin B, a potent isolated compound induces apoptotic signalling pathways and cell cycle arrest in ovarian cancer cells
This study is therefore importance in finding the effective compound that may offer an alternative drug for ovarian cancer treatment. (Source: Apoptosis)
Source: Apoptosis - February 12, 2018 Category: Molecular Biology Source Type: research

Dynamic changes and molecular analysis of cell death in the spinal cord of SJL mice infected with the BeAn strain of Theiler ’s murine encephalomyelitis virus
AbstractTheiler ’s murine encephalomyelitis (TME) is caused by the TME virus (TMEV) and represents an important animal model for multiple sclerosis (MS). Oligodendroglial apoptosis and reduced apoptotic elimination of encephalitogenic leukocytes seem to participate in autoimmune demyelination in MS. The present s tudy quantified apoptotic cells in BeAn–TMEV-induced spinal cord white matter lesions at 14, 42, 98, and 196 days post infection (dpi) using immunostaining. Apoptotic cells were identified by transmission electron microscopy and double-immunofluorescence. The mRNA expression of apoptosis-related g enes...
Source: Apoptosis - February 12, 2018 Category: Molecular Biology Source Type: research

Synergistic effect of the pro-apoptosis peptide kla-TAT and the cationic anticancer peptide HPRP-A1
In this study, a peptide –peptide co-administration therapy between hybrid peptide kla-TAT and cationic anticancer peptide HPRP-A1 was designed to increase the anticancer activity of the combination peptides through synergistic effect. kla is a pro-apoptotic peptide which could induce rapid cancer cell apoptosis by disrup tion the mitochondrial membrane when internalized the cells. To enhance more kla peptides pass through cell membrane, a double improvement strategy was designed by chemically conjugation with cell penetration peptide TAT as well as co-administration with cationic membrane active peptide HPRP-A1, and...
Source: Apoptosis - February 3, 2018 Category: Molecular Biology Source Type: research

Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumors
AbstractPituitary tumors are the most common primary intracranial neoplasms. Humanin (HN) and Rattin (HNr), a rat homolog of HN, are short peptides with a cytoprotective action. In the present study, we aimed to evaluate whether endogenous HNr plays an antiapoptotic role in pituitary tumor cells. Thus, we used RNA interference based on short-hairpin RNA (shRNA) targeted to HNr (shHNr). A plasmid including the coding sequences for shHNr and dTomato fluorescent reporter gene was developed (pUC-shHNr). Transfection of somatolactotrope GH3 cells with pUC-shHNr increased apoptosis, suggesting that endogenous HNr plays a cytopro...
Source: Apoptosis - January 19, 2018 Category: Molecular Biology Source Type: research

Piperazine clubbed with 2-azetidinone derivatives suppresses proliferation, migration and induces apoptosis in human cervical cancer HeLa cells through oxidative stress mediated intrinsic mitochondrial pathway
AbstractPiperazine scaffolds or 2-azetidinone pharmacophores have been reported to show anti-cancer activities and apoptosis induction in different types of cancer cells. However, the mechanistic studies involve in induction of apoptosis addressing these two moieties for human cervical cancer cells remain uncertain. The present study emphasizes on the anti-proliferating properties and mechanism involved in induction of apoptosis for these structurally related azoles derivatives in HeLa cancer cells. 1-Phenylpiperazine clubbed with 2-azetidione derivatives (5a–5h) were synthesized, characterized using various spectros...
Source: Apoptosis - January 18, 2018 Category: Molecular Biology Source Type: research

Negative regulators of cell death pathways in cancer: perspective on biomarkers and targeted therapies
AbstractCancer is a primary cause of human fatality and conventional cancer therapies, e.g., chemotherapy, are often associated with adverse side-effects, tumor drug-resistance, and recurrence. Molecularly targeted therapy, composed of small-molecule inhibitors and immunotherapy (e.g., monoclonal antibody and cancer vaccines), is a less harmful alternative being more effective against cancer cells whilst preserving healthy tissues. Drug-resistance, however, caused by negative regulation of cell death signaling pathways, is still a challenge. Circumvention of negative regulators of cell death pathways or development of pred...
Source: Apoptosis - January 10, 2018 Category: Molecular Biology Source Type: research

Caspase cleavage of Mcl-1 impairs its anti-apoptotic activity and proteasomal degradation in non-small lung cancer cells
AbstractGlobal cleavage of cellular proteins by activated caspases is a hallmark of apoptosis, which causes biochemical collapse of the cell. Recent studies suggest that, rather than completely destroying a protein, caspase cleavage can confer novel characteristics or functions. In this respect, the post-caspase role of Bcl-2 family proteins remains uncharacterized. Here, we showed that Mcl-1, a pro-survival member of the Bcl-2 family, was cleaved by caspase-3 in non-small cell lung cancer (NSCLC) cells undergoing chemotherapeutic agent-triggered apoptosis. Caspase cleavage partially impaired the anti-apoptotic activity of...
Source: Apoptosis - December 18, 2017 Category: Molecular Biology Source Type: research

Caspase cleavage of transcription factor Sp1 enhances apoptosis
AbstractSp1 is a ubiquitous transcription factor that regulates many genes involved in apoptosis and senescence. Sp1 also has a role in the DNA damage response; at low levels of DNA damage, Sp1 is phosphorylated by ATM and localizes to double-strand break sites where it facilitates DNA double-strand-break repair. Depletion of Sp1 increases the sensitivity of cells to DNA damage, whereas overexpression of Sp1 can drive cells into apoptosis. In response to a variety of stimuli, Sp1 can be regulated through proteolytic cleavage by caspases and/or degradation. Here, we show that activation of apoptosis through DNA damage or TR...
Source: Apoptosis - December 13, 2017 Category: Molecular Biology Source Type: research

SDF-1 induces TNF-mediated apoptosis in cardiac myocytes
AbstractChemokines are small secreted proteins with chemoattractant properties that play a key role in inflammation. One such chemokine, Stromal cell-derived factor-1 (SDF-1) also known as CXCL12, and its receptor, CXCR4, are expressed and functional in cardiac myocytes. SDF-1 both stimulates and enhances the cellular signal which attracts potentially beneficial stem cells for tissue repair within the ischemic heart. Paradoxically however, this chemokine is known to act in concert with the inflammatory cytokines of the innate immune response which contributes to cellular injury through the recruitment of inflammatory cells...
Source: Apoptosis - December 13, 2017 Category: Molecular Biology Source Type: research

Correction to: Combined gene expression and proteomic analysis of EGF induced apoptosis in A431 cells suggests multiple pathways trigger apoptosis
AbstractThe original version of this article unfortunately contained a mistake. The affiliation of first author Dr. Ibrahim Alanazi was incorrect. (Source: Apoptosis)
Source: Apoptosis - December 12, 2017 Category: Molecular Biology Source Type: research

Identifying and monitoring neurons that undergo metamorphosis-regulated cell death (metamorphoptosis) by a neuron-specific caspase sensor (Casor) in Drosophila melanogaster
AbstractActivation of caspases is an essential step toward initiating apoptotic cell death. During metamorphosis ofDrosophila melanogaster, many larval neurons are programmed for elimination to establish an adult central nervous system (CNS) as well as peripheral nervous system (PNS). However, their neuronal functions have remained mostly unknown due to the lack of proper tools to identify them. To obtain detailed information about the neurochemical phenotypes of the doomed larval neurons and their timing of death, we generated a new GFP-based caspase sensor (Casor) that is designed to change its subcellular position from ...
Source: Apoptosis - December 9, 2017 Category: Molecular Biology Source Type: research

Molecular docking studies of bioactive compounds from Annona muricata Linn as potential inhibitors for Bcl-2, Bcl-w and Mcl-1 antiapoptotic proteins
AbstractAnnona muricata Linn or usually identified as soursop is a potential anticancer plant that has been widely reported to contain valuable chemopreventive agents known as annonaceous acetogenins. The antiproliferative and anticancer activities of this tropical and subtropical plant have been demonstrated in cell culture and animal studies.A. muricata L. exerts inhibition against numerous types of cancer cells, involving multiple mechanism of actions such as apoptosis, a programmed cell death that are mainly regulated by Bcl-2 family of proteins. Nonetheless, the binding mode and the molecular interactions of the plant...
Source: Apoptosis - December 4, 2017 Category: Molecular Biology Source Type: research

A triazole-conjugated benzoxazone induces reactive oxygen species and promotes autophagic apoptosis in human lung cancer cells
AbstractNumerous approaches suggested that compounds with conjugated triazole moieties or benzoxazone pharmacores are effective to antagonize proliferation of human tumors. The current study reported that a synthetic triazole-conjugated benzoxazone, 4-((5-benzyl-1H-1,2,3-triazol-3-yl)-methyl)-7-methoxy-2H-benzo[b][1,4]-oxazin-3(4H)-one (BTO), inhibited growth rates of human non-small cell lung cancer cells. The cytotoxicity can be enhanced with increasing drug concentrations. More evidence supported that the induced reactive oxygen species lead to ultimate apoptotic cell death by recruiting autophagy. The mechanistic pathw...
Source: Apoptosis - November 28, 2017 Category: Molecular Biology Source Type: research

Linear ubiquitin chain induces apoptosis and inhibits tumor growth
In this study, we surprisingly found that PCNA fused to a head-to-tail linear Ub chain induces apoptosis in a Ub chain length-dependent manner. Further investigation revealed that the apoptotic effect is actually induced by the linear Ub chain independently from PCNA, as the Ub chain fused to GFP or an epitope tag still efficiently induces apoptosis. It is revealed that the artificial linear Ub chain differs from endogenously encoded linear Ub chains in that its Ubs contain a Ub-G76S substitution, making the Ub chain resistant to cleavage by deubiquitination enzymes. We demonstrated in this study that ectopic expression of...
Source: Apoptosis - November 28, 2017 Category: Molecular Biology Source Type: research

Apoptosis turns 21
(Source: Apoptosis)
Source: Apoptosis - November 13, 2017 Category: Molecular Biology Source Type: research

Bromoethylindole (BEI-9) redirects NF- κB signaling induced by camptothecin and TNFα to promote cell death in colon cancer cells
AbstractChemotherapeutic regimens containing camptothecin (CPT), 5-fluorouracil, and oxaliplatin are used to treat advanced colorectal cancer. We previously reported that an indole derivative, 3-(2-bromoethyl)indole (BEI-9), inhibited the proliferation of colon cancer cells and suppressed NF- κB activation. Here, we show that a combination of BEI-9 with either CPT or tumor necrosis factor alpha (TNFα) enhances cell death. Using colorectal cancer cells, we examined the activation of NF-κB by drugs, the potential of BEI-9 for inhibiting drug-induced NF-κB activation, and the enhancemen t of cell death...
Source: Apoptosis - November 8, 2017 Category: Molecular Biology Source Type: research

LncRNA MEG3 inhibit endometrial carcinoma tumorigenesis and progression through PI3K pathway
AbstractLong noncoding RNAs (lncRNAs) are RNA molecules more than 200 nucleotides in length that do not encode proteins. Recent studies have reported increasing numbers of functional lncRNAs. Maternally expressed gene 3 (MEG3) is a maternally imprinted gene encoding an lncRNA that plays a tumor suppressor role in various tumors. However, there has been rare report on mechanism of tumorigenesis and progression of endometrial carcinoma. In the present study, we found significantly lower MEG3 expression in endometrial carcinoma tissues than in normal endometrial tissues. MEG3 overexpression inhibited endometrial cancer cell p...
Source: Apoptosis - November 1, 2017 Category: Molecular Biology Source Type: research

Inhibitors of apoptosis: clinical implications in cancer
AbstractInhibitor of apoptosis (IAP) family comprises a group of endogenous proteins that function as main regulators of caspase activity and cell death. They are considered the main culprits in evasion of apoptosis, which is a fundamental hallmark of carcinogenesis. Overexpression of IAP proteins has been documented in various solid and hematological malignancies, rendering them resistant to standard chemotherapeutics and radiation therapy and conferring poor prognosis. This observation has urged their exploitation as therapeutic targets in cancer with promising pre-clinical outcomes. This review describes the structural ...
Source: Apoptosis - October 24, 2017 Category: Molecular Biology Source Type: research

Procaspase-activating compound-1 induces apoptosis in Trypanosoma cruzi
AbstractSome therapeutics for parasitic, cardiac and neurological diseases activate apoptosis. Therefore, the study of apoptotic proteins in pathogenic organisms is relevant. However, the molecular mechanism of apoptosis in unicellular organisms remain elusive, despite morphological evidence of its occurrence. InTrypanosoma cruzi, the causative agent of Chagas disease, metacaspase 3 (TcMCA3), seems to have a key role in parasite apoptosis. Accordingly, this work provides data concerning TcMCA3 regulation through its interaction with procaspase-activating compound 1 (PAC-1), a procaspase 3 activator. Indeed, PAC-1 reducedT....
Source: Apoptosis - October 20, 2017 Category: Molecular Biology Source Type: research

Remote ischemic preconditioning protects human neural stem cells from oxidative stress
AbstractIn previous clinical trials, we showed that remote ischemic preconditioning (rIPC) reduced myocardial damage in children undergoing treatment for congenital heart defects and postoperative renal failure in patients undergoing abdominal aortic aneurysm surgery. In rabbit experiments, pre-treatment with plasma and plasma dialysate (obtained using 15-kDa cut-off dialysis membrane) from donor rabbits subjected to rIPC similarly protected against cardiac infarction. However, the protective substances containing in rIPC plasma have been unknown. In the present study, we showed that rIPC plasma exerted anti-apoptotic and ...
Source: Apoptosis - September 26, 2017 Category: Molecular Biology Source Type: research

Induction of reactive oxygen species: an emerging approach for cancer therapy
AbstractReactive oxygen species (ROS), a group of ions and molecules, include hydroxyl radicals ( ·OH), alkoxyl radicals, superoxide anion (O2·−), singlet oxygen (1O2) and hydrogen peroxide (H2O2). Hydroxyl radicals and alkoxyl radicals are extremely and highly reactive species respectively. Endogenous ROS are mainly formed in mitochondrial respiratory chain. Low levels of ROS play important roles in regulating biological functions in mammalian cells. However, excess production of ROS can induce cell death by oxidative damaging effects to intracellular biomacromolecules. Cancer cell death types induced ...
Source: Apoptosis - September 21, 2017 Category: Molecular Biology Source Type: research

Anisodamine inhibits endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation in rhabdomyolysis-induced acute kidney injury
This study aimed to investigate the protective effect of anisodamine on rhabdomyolysis-induced acute kidney injury (RIAKI). C57BL/6  J mice, TXNIP−/− and NLRP3−/− (both were C57BL/6  J background) mice were used to construct RIAKI model. Anisodamine administration was performed on RIAKI mice only. Mice were divided into control, TXNIP-KD (knock down), LNPR3-KD, and anisodamine group (n = 15 in each group). The renal injury, renal function, renal tubular cells apoptosis and expression of Caspase-1, ASC, endoplasmic reticulum (ER) stress markers IRE-1α, CHOP, and ATF4, an...
Source: Apoptosis - September 16, 2017 Category: Molecular Biology Source Type: research

The muscle regulatory transcription factor MyoD participates with p53 to directly increase the expression of the pro-apoptotic Bcl2 family member PUMA
AbstractThe muscle regulatory transcription factor MyoD is a master regulator of skeletal myoblast differentiation. We have previously reported that MyoD is also necessary for the elevated expression of the pro-apoptotic Bcl2 family member PUMA, and the ensuing apoptosis, that occurs in a subset of myoblasts induced to differentiate. Herein, we report the identification of a functional MyoD binding site within the extended PUMA promoter. In silico analysis of the murine PUMA extended promoter revealed three potential MyoD binding sites within 2  kb of the transcription start site. Expression from a luciferase reporter...
Source: Apoptosis - September 16, 2017 Category: Molecular Biology Source Type: research

Protodioscin ameliorates oxidative stress, inflammation and histology outcome in Complete Freund ’s adjuvant induced arthritis rats
This study aimed to investigate the effect of protodioscin against Complete Freund ’s adjuvant (CFA)-induced arthritis rats. Rats randomly divided into model groups were injected with CFA, companied with different dose of protodioscin (50, 100, and 200 mg/kg body weight). The histology, changes in biochemical parameters and inflammatory cytokines expression were detected for an ti-inflammation effect evaluation of protodioscin. CFA treatment induced arthritic rats with swelling paw, ankle inflammation, and area of lymphocyte infiltration, upregulated inflammatory cytokines (IL-1β, TNF-α, cyclo-oxygena...
Source: Apoptosis - September 15, 2017 Category: Molecular Biology Source Type: research

Piperlongumine induces G2/M phase arrest and apoptosis in cholangiocarcinoma cells through the ROS-JNK-ERK signaling pathway
In this study, we demonstrated the potential anticancer activity of PL in CCA. PL markedly induced death in CCA cell lines in a dose- and time-dependent manner through the activation of caspase-3 and PARP. PL also stimulated ROS accumulation in CCA. Co-exposure of PL with the ROS scavengerN-acetyl-l-cysteine or GSH completely blocked PL-induced apoptosis in CCA cell lines. Increased p21 via the p53-independent pathway in PL-treated CCA cells led to G2/M phase arrest and cell apoptosis. In addition, the study showed that PL trigger CCA cell lines death through JNK-ERK activation. Furthermore, the different antioxidant capac...
Source: Apoptosis - September 14, 2017 Category: Molecular Biology Source Type: research

Peroxynitrite induces apoptosis of mouse cochlear hair cells via a Caspase-independent pathway in vitro
AbstractPeroxynitrite (ONOO−) is a potent and versatile oxidant implicated in a number of pathophysiological processes. The present study was designed to investigate the effect of ONOO− on the cultured cochlear hair cells (HCs) of C57BL/6 mice in vitro as well as the possible mechanism underlying the action of such an oxidative stress. The in vitro primary cultured cochlear HCs were subjected to different concentrations of ONOO−, then, the cell survival and morphological changes were examined by immunofluorescence and transmission electron microscopy (TEM), the apoptosis was determined by Terminal deoxynu...
Source: Apoptosis - September 12, 2017 Category: Molecular Biology Source Type: research

The induction of apoptosis and autophagy in human hepatoma SMMC-7721 cells by combined treatment with vitamin C and polysaccharides extracted from Grifola frondosa
The objective of this study was to investigate the effect of GFP and vitamin C (VC) alone and in combination on the viability of human hepatocarcinoma SMMC-7721 and HepG2 cells. Studies designed to detect cell apoptosis and autophagy were also conducted to investigate the mechanism. Results from the cell viability assay indicated that a combination of GFP (0.2 or 0.25  mg/mL) and VC (0.3 mmol/L) (GFP/VC) led to 52.73 and 53.93% reduction in cell viability of SMMC-7721 and HepG2 cells separately after 24 h. Flow cytometric analysis indicated that GFP/VC treatment induced cell cycle arrest at the G2/M phase, a...
Source: Apoptosis - September 11, 2017 Category: Molecular Biology Source Type: research

Protective effects of carbenoxolone, an 11 β-HSD1 inhibitor, against chemical induced dry eye syndrome
In this study, the therapeutic effects and underlying mechanisms of topical carbenoxolone, an 11β-HSD1 inhibitor, were investigated in benzalkonium chloride (BAC)-treated human conjunctival epithelial cells and a rat DES model. In the in vitro study, carbenoxolone dose-dependently inhibited cell death and 11β-HSD1 activity in BAC-treated human conjunctival epithelial cel ls. For the in vivo study, carbenoxolone or a solvent was administered to the BAC-induced DES model twice daily. BAC-treated rat eyes showed significant increases in ocular surface damage, a reduction of tears, decrease corneal thickness, corneal...
Source: Apoptosis - September 8, 2017 Category: Molecular Biology Source Type: research

mPGES-1-derived prostaglandin E2 stimulates Stat3 to promote podocyte apoptosis
AbstractWe previously reported that microsomal prostaglandin E synthase-1 (mPGES-1) contributed to adriamycin (Adr)-induced podocyte apoptosis. However, the molecular mechanism remains unclear. Here we studied the role of mPGES-1/PGE2 cascade in activating Stat3 signaling and the contribution of Stat3 in PGE2- and Adr-induced podocyte apoptosis. In murine podocytes, PGE2 dose- and time-dependently increased the phosphorylation of Stat3 in line with the enhanced cell apoptosis and reduced podocyte protein podocin. In agreement with the increased Stat3 phosphorylation, Stat3-derived cytokines including IL-6, IL-17, MCP-1, an...
Source: Apoptosis - September 6, 2017 Category: Molecular Biology Source Type: research

The Btk-dependent PIP5K1 γ lipid kinase activation by Fas counteracts FasL-induced cell death
We report here that Btk negatively regulates, through its tyrosine kinase activity, the FasL-mediated cell death in epithelial cell lines from colon cancer origin. More importantly, we show that Btk interacts not only with Fas but also with the phosphatidylinositol-4-phosphate 5-kinase, PIP5K1 γ, which, upon stimulation by Fas ligand, is responsible of a rapid and transient synthesis of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2). This production requires both the presence and the tyrosine kinase activity of Btk, and participates in the negative regulation of FasL-mediated cell death since knocking down PIP5K1 ...
Source: Apoptosis - September 6, 2017 Category: Molecular Biology Source Type: research

20(S)-25-methoxyl-dammarane-3 β, 12β, 20-triol negatively regulates activation of STAT3 and ERK pathways and exhibits anti-cancer effects in HepG2 cells
AbstractThe pro-inflammatory cytokine interleukin 6 (IL-6), via activating its downstream JAK/STAT3 and Ras/ERK signaling pathways, is involved in cell growth, proliferation and anti-apoptotic activities in various malignancies. To screen inhibitors of IL-6 signaling, we constructed a STAT3 and ERK dual-pathway responsive luciferase reporter vector (Co.RE). Among several candidates, the natural compound 20(S)-25-methoxyl-dammarane-3 β, 12β, 20-triol (25-OCH3-PPD, GS25) was identified to clearly inhibit the luciferase activity of Co.RE. GS25 was confirmed to indeed inhibit activation of both STAT3 and ERK pathways...
Source: Apoptosis - September 1, 2017 Category: Molecular Biology Source Type: research

The immune response to secondary necrotic cells
AbstractWhen apoptotic cells are not cleared in an efficient and timely manner, they progress to secondary necrosis and lose their membrane integrity. This results in a leakage of immunostimulatory, danger associated molecular patterns (DAMPs), similar to accidental (or primary) necrosis. However, primary necrosis is a sudden event with an inadvertent release of almost unmodified DAMPs. Secondary necrotic cells, in contrast, have gone through various modifications during the process of apoptosis. Recent research revealed that the molecules released from the cytoplasm or exposed on the cell surface differ between primary ne...
Source: Apoptosis - August 31, 2017 Category: Molecular Biology Source Type: research

SIRT6 knockout cells resist apoptosis initiation but not progression: a computational method to evaluate the progression of apoptosis
AbstractApoptosis is essential for numerous processes, such as development, resistance to infections, and suppression of tumorigenesis. Here, we investigate the influence of the nutrient sensing and longevity-assuring enzyme SIRT6 on the dynamics of apoptosis triggered by serum starvation. Specifically, we characterize the progression of apoptosis in wild type and SIRT6 deficient mouse embryonic fibroblasts using time-lapse flow cytometry and computational modelling based on rate-equations and cell distribution analysis. We find that SIRT6 deficient cells resist apoptosis by delaying its initiation. Interestingly, once apo...
Source: Apoptosis - August 30, 2017 Category: Molecular Biology Source Type: research

Novel histone deacetylase 8-selective inhibitor 1,3,4-oxadiazole-alanine hybrid induces apoptosis in breast cancer cells
In conclusion, our results clearly demonstrated the efficacy of10b as an anticancer agent against breast cancer. (Source: Apoptosis)
Source: Apoptosis - August 24, 2017 Category: Molecular Biology Source Type: research

Modulation of adenylate cyclase signaling in association with MKK3/6 stabilization under combination of SAC and berberine to reduce HepG2 cell survivability
AbstractCancer cells often have faulty apoptotic pathways resulting in sustenance of survivability, tumour metastasis and resistance to anticancer drugs. Alternate strategies are sought to improve therapeutic efficacy and therefore HepG2 cells were treated withS-allyl-cysteine (SAC) and berberine (BER) to analyze their mechanistic impact upon necroptosis along with its interacting relationship to apoptosis. In the present study we observed that SAC and BER exposure reduced NF κβ nuclear translocation through adenylate cyclase-cAMP-protein kinaseA axis and eventually evaded c-FLIP inhibition. Effective RIP1 k63-p...
Source: Apoptosis - August 23, 2017 Category: Molecular Biology Source Type: research

Glucotoxicity promotes aberrant activation and mislocalization of Ras-related C3 botulinum toxin substrate 1 [Rac1] and metabolic dysfunction in pancreatic islet β-cells: reversal of such metabolic defects by metformin
AbstractEmerging evidence suggests that long-term exposure of insulin-secreting pancreatic β-cells to hyperglycemic (HG; glucotoxic) conditions promotes oxidative stress, which, in turn, leads to stress kinase activation, mitochondrial dysfunction, loss of nuclear structure and integrity and cell apoptosis. Original observations from our laboratory have proposed that Rac1 plays a key reg ulatory role in the generation of oxidative stress and downstream signaling events culminating in the onset of dysfunction of pancreatic β-cells under the duress of metabolic stress. However, precise molecular and cellular mechan...
Source: Apoptosis - August 21, 2017 Category: Molecular Biology Source Type: research

Autophagy inhibits high glucose induced cardiac microvascular endothelial cells apoptosis by mTOR signal pathway
AbstractCardiac microvascular endothelial cells (CMECs) dysfunction is an important pathophysiological event in the cardiovascular complications induced by diabetes. However, the underlying mechanism is not fully clarified. Autophagy is involved in programmed cell death. Here we investigated the potential role of autophagy on the CMECs injury induced by high glucose. CMECs were cultured in normal or high glucose medium for 6, 12 and 24  h respectively. The autophagy of CMECs was measured by green fluorescence protein (GFP)-LC3 plasmid transfection. Moreover, the apoptosis of CMEC was determined by flow cytometry. Furt...
Source: Apoptosis - August 20, 2017 Category: Molecular Biology Source Type: research

Erratum to: A novel tubulin polymerization inhibitor, MPT0B206, downregulates Bcr-Abl expression and induces apoptosis in imatinib-sensitive and imatinib-resistant CML cells
(Source: Apoptosis)
Source: Apoptosis - August 18, 2017 Category: Molecular Biology Source Type: research

Lysophosphatidic acid enhances human umbilical cord mesenchymal stem cell viability without differentiation via LPA receptor mediating manner
In this study we aimed to explore the effects of LPA on the survival and differentiation of MSCs and its availability in cell therapy. We found that LPA stimulated hUC-MSC proliferation and protected hUC-MSCs from lipopolysaccharide (LPS) induced apoptosis. We also observed that CD29, CD44, CD73, CD90 and CD105 were expressed, whereas CD34 and CD45 were not expressed in hUC-MSCs, and these makers have no change in LPA containing medium, which indicated that LPA accelerated the survival of hUC-MSCs in an undifferentiating status. We also demonstrated that higher expressed LPAR1 involved in LPA stimulated cell survival actio...
Source: Apoptosis - August 1, 2017 Category: Molecular Biology Source Type: research