Maslinic acid differentially exploits the MAPK pathway in estrogen-positive and triple-negative breast cancer to induce mitochondrion-mediated, caspase-independent apoptosis
AbstractBreast cancer accounts for 1.4 million new cases every year. Triple-negative breast cancer (TNBC) is one the leading cause of mortality in developing countries and is associated with early age onset (under 40  years old). Chemotherapy has a poor success rate in patients with TNBC as compared to other types of breast cancers. It is due to the lack of expression of three validated molecular markers for breast cancer, the estrogen and progesterone receptors, and the amplification of HER-2/Neu. Therefore, a clear need exists for a greater understanding of TNBC at all levels and for the development of better therap...
Source: Apoptosis - September 17, 2020 Category: Molecular Biology Source Type: research

The function and mechanism of ferroptosis in cancer
AbstractFerroptosis is a newly defined form of regulated cell death (RCD) characterized by iron overload, lipid reactive oxygen species (ROS) accumulation, and lipid peroxidation, which is different from necrosis, apoptosis, autophagy and other forms of RCD in morphology, biochemistry, function and gene expression. Increasing evidence has shown that ferroptosis is intimately associated with cancer initiation, progression, and suppression. In this review, we summarize the primary mechanisms and signal pathways relevant to ferroptosis and then discuss the potential roles of ferroptosis in cancer, including those related to p...
Source: Apoptosis - September 17, 2020 Category: Molecular Biology Source Type: research

RAB25 confers resistance to chemotherapy by altering mitochondrial apoptosis signaling in ovarian cancer cells
AbstractOvarian cancer remains one of the most frequent causes of cancer-related death in women. Many patients with ovarian cancer suffer from de novo or acquired resistance to chemotherapy. Here, we report that RAB25 suppresses chemotherapy-induced mitochondrial apoptosis signaling in ovarian cancer cell lines and primary ovarian cancer cells. RAB25 blocks chemotherapy-induced apoptosis upstream of mitochondrial outer membrane permeabilization by either increasing antiapoptotic BCL-2 proteins or decreasing proapoptotic BCL-2 proteins. In particular, BAX expression negatively correlates with RAB25 expression in ovarian can...
Source: Apoptosis - September 8, 2020 Category: Molecular Biology Source Type: research

Epoxyazadiradione exhibit activities in head and neck squamous cell carcinoma by targeting multiple pathways
AbstractThe head and neck squamous cell carcinoma (HNSCC) constitute about 90% of all head and neck cancers. HNSCC falls in the top 10 cancers in men globally. Epoxyazadiradione (EPA) and Azadiradione (AZA) are the limonoids derived from the medicinal plantAzadirachta indica (popularly known as Neem). Whether or not the limonoids exhibit activities against HNSCC and the associated mechanism remains elusive. Herein, we demonstrate that EPA exhibits stronger activity in HNSCC in comparison to AZA. The limonoids obeyed the Lipinski ’s rule of 5. EPA exhibited activities in a variety of HNSCC lines like suppression of th...
Source: Apoptosis - September 7, 2020 Category: Molecular Biology Source Type: research

Interconnections among major forms of regulated cell death
AbstractAs a basic biological phenomenon of cells, regulated cell death (RCD) has irreplaceable influence on the occurrence and development of many processes of life and diseases. RCD plays an important role in the stability of the homeostasis, the development of multiple systems and the evolution of organisms. Thus comprehensively understanding of RCD is undoubtedly helpful in the innovation of disease treatment. Recently, research on the underlying mechanisms of the major forms of RCD, such as apoptosis, autophagy, necroptosis, pyroptosis, paraptosis and neutrophils NETosis has made significant breakthroughs. In addition...
Source: Apoptosis - September 5, 2020 Category: Molecular Biology Source Type: research

Photodynamic therapy: apoptosis, paraptosis and beyond
AbstractPhotodynamic therapy (PDT) is a light-catalyzed process that can initiate cellular death pathways from the formation of cytotoxic reactive oxygen species at sub-cellular sites. Apoptosis was the first such pathway to be identified. Autophagy can also occur and is often found to be cytoprotective. Another process termed paraptosis can also have lethal consequences, even in cells with an impaired apoptotic pathway. PDT in vivo can evoke other potentially cytotoxic processes including vascular shutdown and enhanced immunologic recognition of neoplastic cells. Using appropriate photosensitizing agents, sub-cellular PDT...
Source: Apoptosis - September 4, 2020 Category: Molecular Biology Source Type: research

Neuroprotective effect of 3,3 ’-Diindolylmethane against perinatal asphyxia involves inhibition of the AhR and NMDA signaling and hypermethylation of specific genes
In this study, we demonstrated for the first time the neuroprotective capacity of 3,3’-diindolylmethane (DIM) in an in vivo model of rat perinatal asphyxia, which has translational value and corresponds to hypoxic/ischemic episodes in human newborns. Posttreatment with DIM restored the weight of the ipsilateral hemisphere and normalized cell number in the brain structures of rats exposed to perinatal asphyxia. DIM also downregulated the mRNA e xpression of HIF1A-regulatedBnip3 andHif1a which is a hypoxic marker, and the expression of miR-181b which is an indicator of perinatal asphyxia. In addition, DIM inhibited apo...
Source: Apoptosis - August 20, 2020 Category: Molecular Biology Source Type: research

Letter to the editor: iron, apoptosis, and ferroptosis
(Source: Apoptosis)
Source: Apoptosis - August 7, 2020 Category: Molecular Biology Source Type: research

Acetylcholinesterase promotes apoptosis in insect neurons
AbstractApoptosis plays a major role in development, tissue renewal and the progression of degenerative diseases. Studies on various types of mammalian cells reported a pro-apoptotic function of acetylcholinesterase (AChE), particularly in the formation of the apoptosome and the degradation of nuclear DNA. While three AChE splice variants are present in mammals, invertebrates typically express twoache genes that code for a synaptically located protein and a protein with non-synaptic functions respectively. In order to investigate a potential contribution of AChE to apoptosis in insects, we selected the migratory locustLocu...
Source: Apoptosis - August 5, 2020 Category: Molecular Biology Source Type: research

Regulatory T cells are less sensitive to glucocorticoid hormone induced apoptosis than CD4 + T cells
AbstractEarlier we have reported that thymic regulatory T cells (Treg) are resistant to in vivo glucocorticoid hormone (GC)-induced apoptosis, while the most GC-sensitive DP thymocytes died through the activation of mitochondrial apoptotic pathway. Here we analyzed the apoptosis-inducing effect of high dose (10–6 M) in vitro dexamethasone (DX) treatment in mouse thymic- and splenic Tregs and CD4+ T cells. Activation of both extrinsic and intrinsic apoptotic pathways started after 2  h of DX treatment in CD4 SP thymocytes and was 3 × higher than in CD4+ splenocytes, while in Treg cells, w...
Source: Apoptosis - July 31, 2020 Category: Molecular Biology Source Type: research

BAX-dependent mitochondrial pathway mediates the crosstalk between ferroptosis and apoptosis
In this study, we investigated a possible mechanism of this interplay between ferroptosis and apoptosis. Results from our studies reveal that combined treatment of the ferroptotic agent erastin and the apoptotic agent TRAIL effectively disrupted mitochondrial membrane potential ( ΔΨm) and subsequently promoted caspase activation. The alterations of mitochondrial membrane potential are probably due to an increase in oligomerization of BAX and its accumulation at the mitochondria during treatment with erastin and TRAIL. Interestingly, the combined treatment-promoted apoptosi s was effectively inhibited in BAX-defic...
Source: Apoptosis - July 31, 2020 Category: Molecular Biology Source Type: research

Valproic acid upregulates the expression of the p75NTR/sortilin receptor complex to induce neuronal apoptosis
AbstractThe antiepileptic and mood stabilizer agent valproic acid (VPA) has been shown to exert anti-tumour effects and to cause neuronal damage in the developing brain through mechanisms not completely understood. In the present study we show that prolonged exposure of SH-SY5Y and LAN-1 human neuroblastoma cells to clinically relevant concentrations of VPA caused a marked induction of the protein and transcript levels of the common neurotrophin receptor p75NTR and its co-receptor sortilin, two promoters of apoptotic cell death in response to proneurotrophins. VPA induction of p75NTR and sortilin was associated with an inc...
Source: Apoptosis - July 25, 2020 Category: Molecular Biology Source Type: research

Correction to: A potent protective effect of baicalein on liver injury by regulating mitochondria-related apoptosis
The original version of this article unfortunately contains errors in methods and figures. In methods, animal experiments part: “2 ml/kg” and “after two days” were described incorrectly which were actually “4 ml/kg” and “after eight days” respectively. (Source: Apoptosis)
Source: Apoptosis - July 18, 2020 Category: Molecular Biology Source Type: research

In S. cerevisiae hydroxycitric acid antagonizes chronological aging and apoptosis regardless of citrate lyase
AbstractCaloric restriction mimetics (CRMs) are promising molecules to prevent age-related diseases as they activate pathways driven by a true caloric restriction. Hydroxycitric acid (HCA) is considered a bona fide CRM since it depletes acetyl-CoA pools by acting as a competitive inhibitor of ATP citrate lyase (ACLY), ultimately repressing protein acetylation and promoting autophagy. Importantly, it can reduce inflammation and tumour development. In order to identify phenotypically relevant new HCA targets we have investigated HCA effects inSaccharomyces cerevisiae, where ACLY is lacking. Strikingly, the drug revealed a po...
Source: Apoptosis - July 14, 2020 Category: Molecular Biology Source Type: research

The specific PKC- α inhibitor chelerythrine blunts costunolide-induced eryptosis
AbstractCostunolide, a natural sesquiterpene lactone, has multiple pharmacological activities such as neuroprotection or induction of apoptosis and eryptosis. However, the effects of costunolide on pro-survival factors and enzymes in human erythrocytes, e.g. glutathione and glucose-6-phosphate dehydrogenase (G6PDH) respectively, have not been studied yet. Our aim was to determine the mechanisms underlying costunolide-induced eryptosis and to reverse this process. Phosphatidylserine exposure was estimated from annexin-V-binding, cell volume from forward scatter in flow cytometry, and intracellular glutathione [GSH]i from hi...
Source: Apoptosis - July 7, 2020 Category: Molecular Biology Source Type: research

Elevated IL-22 in psoriasis plays an anti-apoptotic role in keratinocytes through mediating Bcl-xL/Bax
In this study, we found that IL-22/IL-22R1 in lesional skin and IL-22 in serum from psoriatic patients were highly upregulated compared with healthy controls, while IL-22BP was not changed. Correlations between IL-22/IL-22R1 levels and the thickness of psoriatic lesions suggested that IL-22 might positively regulate abnormal hyperplasia in psoriasis. Apoptotic keratinocytes were increased only in stratum corneum, but not in spinous and basal layers of psoriasis. Moreover, IL-22 promoted cell viability in human epidermal keratinocytes (HEKs). The apoptosis induced by TNF- α and IFN-γ was inhibited in HEKs treate...
Source: Apoptosis - July 6, 2020 Category: Molecular Biology Source Type: research

Cytokine regulation of apoptosis-induced apoptosis and apoptosis-induced cell proliferation in vascular smooth muscle cells
We examined the consequences of VSMC apoptosis after activating extrinsic and intrinsic death pathways. VSMCs undergoing apoptosis through Fas/CD95 or the protein kinase inhibitor staurosporine transcriptionally activated interleukin 6 (IL-6) and granulocyte-macrophage colony stimulating factor (GM-CSF), leading to their secretion. Apoptosis induced activation of p38MAPK, JNK, and Akt, but neither p38 and JNK activation nor IL-6 or GM-CSF induction required caspase cleavage. IL-6 induction depended upon p38 activity, while Fas-induced GM-CSF expression required p38 and JNK. Conditioned media from apoptotic VSMCs induced VS...
Source: Apoptosis - July 5, 2020 Category: Molecular Biology Source Type: research

Rational design of genetically encoded reporter genes for optical imaging of apoptosis
AbstractApoptosis is a process in which cells are genetically regulated to cause a series of changes in morphology and metabolic activity, which ultimately lead to cell death. Apoptosis plays a vital role in the entire life cycle of an organism. Too much or too little apoptosis can cause a variety of diseases. Therefore, efficient and convenient methods for detecting apoptosis are necessary for clinical treatment and drug development. Traditional methods for detecting apoptosis may cause damage to the body during sample collection, such as for flow cytometry analysis. So it is necessary to monitor apoptosis without invasio...
Source: Apoptosis - July 4, 2020 Category: Molecular Biology Source Type: research

Antiproliferative effect of bacterial cyclodipeptides in the HeLa line of human cervical cancer reveals multiple protein kinase targeting, including mTORC1/C2 complex inhibition in a TSC1/2-dependent manner
AbstractCervix adenocarcinoma rendered by human papillomavirus (HPV) integration is an aggressive cancer that occurs by dysregulation of multiple pathways, including oncogenes, proto-oncogenes, and tumor suppressors. The PI3K/Akt/mTOR pathway, which cross-talks with the Ras –ERK pathway, has been associated with cervical cancers (CC), which includes signaling pathways related to carcinoma aggressiveness, metastasis, recurrence, and drug resistance. Since bacterial cyclodipeptides (CDPs) possess cytotoxic properties in HeLa cells with inhibiting Akt/S6k phosphorylatio n, the mechanism of CDPs cytotoxicity involved was...
Source: Apoptosis - July 2, 2020 Category: Molecular Biology Source Type: research

Cardiac  Mitochondrial PTEN-L determines cell fate between apoptosis and survival during chronic alcohol consumption
AbstractChronic alcohol consumption induces myocardial damage and a type of non-ischemic cardiomyopathy termed alcoholic cardiomyopathy, where mitochondrial ultrastructural damages and suppressed fusion activity promote cardiomyocyte apoptosis. The aim of the present study is to determine the role of mitochondrial fission proteins and/or other proteins that localise on cardiac mitochondria for apoptosis upon ethanol consumption. In vivo and in vitro chronic alcohol exposure increased mitochondrial Drp1 levels but knockdown of the same did not confer cardioprotection in H9c2 cells. These cells displayed downregulated expres...
Source: Apoptosis - June 26, 2020 Category: Molecular Biology Source Type: research

The therapeutic strategy of drug re-positioning to induce autophagic cell death in brain malignancy
(Source: Apoptosis)
Source: Apoptosis - June 24, 2020 Category: Molecular Biology Source Type: research

The α7 and β2 nicotinic acetylcholine receptor subunits regulate apoptosis in the infant hippocampus, and in sudden infant death syndrome (SIDS)
AbstractApoptosis is increased in the hippocampus of infants who died of sudden infant death syndrome (SIDS), yet it is not known via which mechanism this has occurred. Following existing support for a role of the α7 and β2 nicotinic acetylcholine receptor (nAChR) subunits in apoptotic regulation, we aimed to determine whether these subunits are altered in the SIDS hippocampus and if they are correlated with cell death markers of active caspase-3 (Casp-3) and TUNEL. Further analyses were run according to t he presence of major SIDS risk factors related to hypoxia (bed-sharing and prone sleeping), infection ...
Source: Apoptosis - June 23, 2020 Category: Molecular Biology Source Type: research

The pro-apoptotic ARTS protein induces neutrophil apoptosis, efferocytosis, and macrophage reprogramming to promote resolution of inflammation
AbstractARTS (Sept4_i2) is a pro-apoptotic protein and a product of the Sept4 gene. ARTS acts upstream of mitochondria to initiate caspase activation. ARTS induces apoptosis by specifically binding XIAP and allowing de-repression of active caspases required for Mitochondrial Outer Membrane Permeabilzation (MOMP). Moreover, ARTS promotes apoptosis by inducing ubiquitin-mediated degradation of both major anti-apoptotic proteins XIAP and Bcl-2. In the resolution phase of inflammation, the infiltrating leukocytes, which execute the acute innate response, undergo apoptosis and are subsequently cleared by phagocytic macrophages ...
Source: Apoptosis - June 20, 2020 Category: Molecular Biology Source Type: research

Cytosolic DNA sensing through cGAS and STING is inactivated by gene mutations in pangolins
AbstractThe release of DNA into the cytoplasm upon damage to the nucleus or during viral infection triggers an interferon-mediated defense response, inflammation and cell death. In human cells cytoplasmic DNA is sensed by cyclic GMP-AMP Synthase (cGAS) and Absent In Melanoma 2 (AIM2). Here, we report the identification of a “natural knockout” model of cGAS. Comparative genomics of phylogenetically diverse mammalian species showed that cGAS and its interaction partner Stimulator of Interferon Genes (STING) have been inactivated by mutations in the Malayan pangolin whereas other mammals retained intact copies of ...
Source: Apoptosis - June 12, 2020 Category: Molecular Biology Source Type: research

Flow cytometric detection of hyper-polarized mitochondria in regulated and accidental cell death processes
AbstractShikonin induced necroptosis in Jurkat cells were  identified flow cytometrically by the up-regulation of RIP3 in live cells and that a proportion of these cells underwent other forms of regulated cell death (RCD) which included parthanatos (  40%), or cleaved PARP (>  15%) but less DNA Damage (
Source: Apoptosis - June 3, 2020 Category: Molecular Biology Source Type: research

Combination of a p53-activating CP-31398 and an MDM2 or a FAK inhibitor produces growth suppressive effects in mesothelioma with wild-type p53 genotype
We examined a growth suppressive activity of CP-31398 which was developed to restore the p53 functions irrespective of the genotype in mesothelioma with wild-type or mutatedp53. CP-31398 up-regulated p53 levels in cells with wild-typep53 genotype but induced cell growth suppression in a p53-independent manner. In contrasts, nutlin-3a, an MDM2 inhibitor, increased p53 and p21 levels in mesothelioma with the wild-typep53 genotype and produced growth suppressive effects. We investigated a combinatory effect of CP-31398 and nutlin-2a and found the combination produced synergistic growth inhibition in mesothelioma with the wild...
Source: Apoptosis - May 28, 2020 Category: Molecular Biology Source Type: research

Activation of β1 integrins and caveolin-1 by TF/FVIIa promotes IGF-1R signaling and cell survival
In conclusion, we present a plausible mechanism for the interplay between TF and IGF-1R involving FVIIa, β1-integrins, Src family proteins, and caveolin-1. Our results increase the knowledge of diseases associated with TF and IGF-1R overexpression in general but specifically of TF-mediated signaling with focus on cell survival. (Source: Apoptosis)
Source: Apoptosis - May 27, 2020 Category: Molecular Biology Source Type: research

Smac mimetics can provoke lytic cell death that is neither apoptotic nor necroptotic
AbstractSmac mimetics, or IAP antagonists, are a class of drugs currently being evaluated as anti-cancer therapeutics. These agents antagonize IAP proteins, including cIAP1/2 and XIAP, to induce cell death via apoptotic or, upon caspase-8 deficiency, necroptotic cell death pathways. Many cancer cells are unresponsive to Smac mimetic treatment as a single agent but can be sensitized to killing in the presence of the cytokine TNF α, provided either exogenously or via autocrine production. We found that high concentrations of a subset of Smac mimetics could provoke death in cells that did not produce TNFα, despite...
Source: Apoptosis - May 21, 2020 Category: Molecular Biology Source Type: research

Upregulation of microRNA-532 enhances cardiomyocyte apoptosis in the diabetic heart
In this study, we sought to determine whether diabetes induces dysregulation of miR-532 and if this is associated with accentuated apoptosis. RT-PCR analysis showed a significant increase in miR-532 expression in the right atrial appendage tissue of type 2 diabetic patients undergoing coronary artery bypass graft surgery. This was associated with marked downregulation of its anti-apoptotic target protein apoptosis repressor with caspase recruitment domain (ARC) and increased TUNEL positive cardiomyocytes. Further analysis showed a positive correlation between apoptosis and miR-532 levels. Time-course experiments in a mouse...
Source: Apoptosis - May 16, 2020 Category: Molecular Biology Source Type: research

Doxorubicin sensitizes cancer cells to Smac mimetic via synergistic activation of the CYLD/RIPK1/FADD/caspase-8-dependent apoptosis
AbstractSmac/Diablo is a pro-apoptotic protein via interaction with inhibitors of apoptosis proteins (IAPs) to relieve their inhibition of caspases. Smac mimetic compounds (also known as antagonists of IAPs) mimic the function of Smac/Diablo and sensitize cancer cells to TNF-induced apoptosis. However, the majority of cancer cells are resistant to Smac mimetic alone. Doxorubicin is a widely used chemotherapeutic drug and causes adverse effect of cardiotoxicity in many patients. Therefore, it is important to find strategies of combined chemotherapy to increase chemosensitivity and reduce the adverse effects. Here, we report...
Source: Apoptosis - May 16, 2020 Category: Molecular Biology Source Type: research

A potent protective effect of baicalein on liver injury by regulating mitochondria-related apoptosis
In this study, we aim to investigate the protective effects of baicalein on liver injury induced by oxidative stress. H2O2 and CCl4 were employed to establish liver injury models in vivo and in vitro, respectively. The protective effect of baicalein on oxidative stress –induced liver injury was evaluated by detecting the mitochondrial dynamics, the level of autophagy and apoptosis, the histopathology of liver, the indicators of liver function, and the level of oxidative stress in vitro and in vivo. March5 is the key regulator during liver injury induced by oxida tive stress. March5 can ubiquitinate Drp1 and promote D...
Source: Apoptosis - May 14, 2020 Category: Molecular Biology Source Type: research

Hemocompatible LAT1-inhibitor can induce apoptosis in cancer cells without affecting brain amino acid homeostasis
In this study, a previously reported LAT1-inhibitor (KMH-233) was studied for its hemocompatibility and toxicity towards human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (AoSMCs). Furthermore, the cytotoxic effects against human breast adenocarcinoma cells (MCF-7) and its ability to affect mammalian (or mechanistic) target of rapamycin (mTOR) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κB) signaling were evaluated. Moreover, the effects of this inhibitor to modulate LAT1 function on the cell surface and the brain amino acid homeostasis were evaluated afte...
Source: Apoptosis - May 13, 2020 Category: Molecular Biology Source Type: research

Gedunin isolated from the mangrove plant Xylocarpus granatum exerts its anti-proliferative activity in ovarian cancer cells through G2/M-phase arrest and oxidative stress-mediated intrinsic apoptosis
AbstractGedunin is a natural tetranorterpenoid secondary metabolite found in plants of the Meliaceae family, which has been reported for its antiparasitic, antifungal and anticancer activities. Here, we describe the molecular mechanisms underlying the in vitro anti proliferative activity of gedunin (isolated from the mangrove plantXylocarpus granatum) in human ovarian cancer cells. We observed that gedunin triggered severe ROS generation leading to DNA damage and cell cycle arrest in G2/M phase thus inhibiting cell proliferation. ROS upregulation also led to mitochondrial stress and membrane depolarization, which eventuall...
Source: Apoptosis - May 13, 2020 Category: Molecular Biology Source Type: research

Citarinostat and Momelotinib co-target HDAC6 and JAK2/STAT3 in lymphoid malignant cell lines: a potential new therapeutic combination
AbstractHistone deacetylase (HDAC) inhibitors represent an encouraging class of antitumor drugs. HDAC inhibitors induce a series of molecular and biological responses and minimal toxicity to normal cells. Citarinostat (Acy-241) is a second generation, orally administered, HDAC6-selective inhibitor. Momelotinib (CYT387) is an orally administered inhibitor of Janus kinase/signal transducer of transcription-3 (JAK/STAT3) signaling. Momelotinib showed efficacy in patients with myelofibrosis. We hypothesized that both HDAC and JAK/STAT pathways were important in lymphoproliferative disorders, and that inhibiting JAK/STAT3 and H...
Source: Apoptosis - May 11, 2020 Category: Molecular Biology Source Type: research

The function of RNase L and its degradation mechanism in cardiac acute ischemic injury
In this study, we tested the hypothesis that RNase L may be involved in the pathological process of cardiac ischemic injury. RNase L-overexpressing and RNase L knockdown H9c2 cell lines were subjected to the oxygen and glucose deprivation (OGD) model, and RNase L knockout mice were subjected to acute myocardial infarction surgical procedures to investigate the function of RNase L in ischemic heart injury. OGD induced abnormal aggregation of double-stranded RNA in H9c2 cells, activated RNase L within 6  h of OGD initiation, and mediated apoptosis via the c-Jun N-terminal kinase pathway. In addition, RNase L knockout mi...
Source: Apoptosis - May 8, 2020 Category: Molecular Biology Source Type: research

Baicalein attenuates caspase-independent cells death via inhibiting PARP-1 activation and AIF nuclear translocation in cerebral ischemia/reperfusion rats
AbstractIt is reported that baicalein can activate PI3K/AKT pathway, inhibit caspase activation and reduce cerebral infarct volume in middle cerebral artery occlusion (MCAO) rats. However, a caspase-independent mechanism initiated by poly (ADP-ribose) polymerase-1 (PARP-1) activation has been reported to make more contribution to cells death after ischemic stroke. In the present study, we established a cerebral ischemia/reperfusion (I/R) rat model through middle cerebral artery occlusion following reperfusion to investigate the mechanisms of ischemic tissue recovery following baicalein treatment. The data showed that baica...
Source: Apoptosis - April 27, 2020 Category: Molecular Biology Source Type: research

BCL-2 family deregulation in colorectal cancer: potential for BH3 mimetics in therapy
AbstractApoptosis is a form of programmed cell death that is essential for tissue homeostasis. De-regulation of the balance between proliferation and apoptosis contributes to tumor initiation. Particularly in the colon where apoptosis is a crucial process in intestinal turnover, inhibition of apoptosis facilitates transformation and tumor progression. The BCL-2 family of proteins are key regulators of apoptosis and have been implicated in colorectal cancer (CRC) initiation, progression and resistance to therapy. In this review we outline the current knowledge on the BCL-2 family-regulated intrinsic apoptosis pathway and me...
Source: Apoptosis - April 25, 2020 Category: Molecular Biology Source Type: research

Soluble receptor for advanced glycation end-products promotes angiogenesis through activation of STAT3 in myocardial ischemia/reperfusion injury
AbstractSoluble receptor for advanced glycation end-products (sRAGE), which exerts cardioprotective effect through inhibiting cardiomyocyte apoptosis and autophagy during ischemia/reperfusion (I/R) injury, is also known to enhance angiogenesis in post-ischemic reperfusion injury-critical limb ischemia (PIRI-CLI) mice. However, whether sRAGE protects the heart from myocardial I/R injury via promoting angiogenesis remains unclear. Myocardial model of I/R injury was conducted by left anterior descending (LAD) ligation for 30 min and reperfusion for 2 weeks in C57BL/6 mice. And I/R injury in cardiac microvascular endothelial c...
Source: Apoptosis - April 24, 2020 Category: Molecular Biology Source Type: research

miR-21 protects neonatal rats from hypoxic-ischemic brain damage by targeting CCL3
AbstractHypoxic-ischemic brain damage (HIBD) represents one of the leading causes of neonatal mortality and permanent neurological disability worldwide. Compelling studies have identified implication of microRNAs (miRNAs) in HIBD. However, the molecular mechanism of miR-21 underlying the disease pathogenesis is unknown. The present study aims to explore the role of miR-21 in neonatal rats with HIBD. HIBD rat models were developed by carotid artery ligation and hypoxia treatment, and in vitro cell models were induced by oxygen –glucose deprivation. Through RT-qPCR and western blot analysis, high expression of CCL3 and...
Source: Apoptosis - April 18, 2020 Category: Molecular Biology Source Type: research

Glucocorticoid-induced autophagy and apoptosis in bone
AbstractGlucocorticoids are widely prescribed to treat various allergic and autoimmune diseases; however, long-term use results in glucocorticoid-induced osteoporosis, characterized by consistent changes in bone remodeling with decreased bone formation as well as increased bone resorption. Not only bone mass but also bone quality decrease, resulting in an increased incidence of fractures. The primary role of autophagy is to clear up damaged cellular components such as long-lived proteins and organelles, thus participating in the conservation of different cells. Apoptosis is the physiological death of cells, and plays a cru...
Source: Apoptosis - March 10, 2020 Category: Molecular Biology Source Type: research

Programmed death, cells on the last train to glory
(Source: Apoptosis)
Source: Apoptosis - March 7, 2020 Category: Molecular Biology Source Type: research

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway
AbstractOur previous studies have shown that abdominal paracentesis drainage (APD) is a safe and effective strategy for patients with severe acute pancreatitis (SAP). However, the underlying mechanisms behind APD treatment remain poorly understood. Given that apoptosis is a critical pathological response of SAP, we here aim to investigate the effect of APD on cell apoptosis in pancreatic tissues during SAP and to explore its potential molecular mechanism. SAP was induced by 5% sodium-taurocholate retrograde while APD group was inserted a drainage tube into the right lower abdomen of rats immediately after SAP induction. Hi...
Source: Apoptosis - February 25, 2020 Category: Molecular Biology Source Type: research

BRAFi induced demethylation of miR-152-5p regulates phenotype switching by targeting TXNIP in cutaneous melanoma
AbstractTreatment of advanced BRAFV600-mutant melanoma using BRAF inhibitors (BRAFi) eventually leads to drug resistance and selects for highly metastatic tumor cells. We compared the most differentially dysregulated miRNA expression profiles of vemurafenib-resistant and highly-metastatic melanoma cell lines obtained from GEO DataSets. We discovered miR-152-5p was a potential regulator mediating melanoma drug resistance and metastasis. Functionally, knockdown of miR-152-5p significantly compromised the metastatic ability of BRAFi-resistant melanoma cells and overexpression of miR-152-5p promoted the formation of slow-cycli...
Source: Apoptosis - February 13, 2020 Category: Molecular Biology Source Type: research

Exploitation of a novel phenothiazine derivative for its anti-cancer activities in malignant glioblastoma
This study adopts a drug repurposing approach by investigating the anti-cancer activity of a derivative of the antipsychotic drug phenothiazine (DS00329) in malignant U251 and U87 glioblastoma cells. Results from MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and clonogenic assays showed that DS00329 inhibited short-term glioblastoma cell viability and long-term survival while sparing non-cancerous cells. Western  blot analysis with an antibody to γH2AX showed that DS00329 induced DNA damage and flow cytometry and western blotting confirmed that it triggered a G1 cell cycle arrest which corre...
Source: Apoptosis - February 8, 2020 Category: Molecular Biology Source Type: research

Potent antitumor activity of oncolytic adenovirus expressing C/EBP β against hepatocellular carcinoma
(Source: Apoptosis)
Source: Apoptosis - February 5, 2020 Category: Molecular Biology Source Type: research

Synergism of 4HPR and SAHA increases anti-tumor actions in glioblastoma cells
AbstractGlioblastoma is the most malignant and prevalent brain tumor in adults. It can grow and spread quickly causing harm to the brain health. One of the major challenges in treatment of glioblastoma is drug resistance. Use of synergistic combination of two drugs with different anti-tumor effects is nowadays highly considered in the development of effective therapeutic strategies for many malignancies. In the present study, we showed synergistic therapeutic efficacies of two chemical compounds,N-(4-hydroxyphenyl) retinamide (4HPR) and suberoylanilide hydroxamic acid (SAHA), for significant reduction in cell viability of ...
Source: Apoptosis - January 31, 2020 Category: Molecular Biology Source Type: research

Loss of BIM in T cells results in BCL-2 family BH3-member compensation but incomplete cell death sensitivity normalization
This study further highlights the importance of BIM in cell death maintenance in T cells and provides new insight into the dynamism underlying BH3-only regulation of T cell homeostasis versus induced cell death and suggests that CD4+ and CD8+ T cells compensate differently in response to loss ofBim. (Source: Apoptosis)
Source: Apoptosis - January 28, 2020 Category: Molecular Biology Source Type: research

Lactate accelerates vascular calcification through NR4A1-regulated mitochondrial fission and BNIP3-related mitophagy
This study suggests that the NR4A1/DNA-PKcs/p53 pathway is involved in the mechanism by which lactate accelerates vascular calcification, partly through excessive Drp-mediated mitochondrial fission and BNIP3-related mitophagy deficiency. (Source: Apoptosis)
Source: Apoptosis - January 28, 2020 Category: Molecular Biology Source Type: research

DDX3 modulates cisplatin resistance in OSCC through ALKBH5-mediated m 6 A-demethylation of FOXM1 and NANOG
In this study we found genetic (shRNA) or pharmacological (ketorolac salt) inhibition of DDX3 reduced CSC population by suppressing the expression of FOXM1 and NANOG. We also found that m6A demethylase ALKBH5 is directly regulated by DDX3 which leads to decreased m6A methylation in FOXM1 and NANOG nascent transcript that contribute to chemoresistance. Here, we found DDX3 expression was upregulated in both cisplatin-resistant OSCC lines and chemoresistant tumors when compared with their respective sensitive counterparts. In a patient-derived cell xenograft model of chemoresistant OSCC, ketorolac salt restores cisplatin-medi...
Source: Apoptosis - January 23, 2020 Category: Molecular Biology Source Type: research

microRNA-499a promotes the progression and chemoresistance of cervical cancer cells by targeting SOX6
AbstractEmerging evidence has indicated that microRNAs are involved in multiple processes of cancer development. Previous studies have demonstrated that microRNA-499a (miR-499a) plays both oncogenic and tumor suppressive roles in several types of malignancies, and genetic variants in miR-499a are associated with the risk of cervical cancer. However, the biological roles of miR-499a in cervical cancer have not been investigated. Quantitative real-time PCR was used to assess miR-499a expression in cervical cancer cells. Mimics or inhibitor of miR-499a was transfected into cervical cancer cells to upregulate or downregulate m...
Source: Apoptosis - January 14, 2020 Category: Molecular Biology Source Type: research