Form Of Programmed Cell Death Research Articles

Detection of Apoptosis-like Cell Death in Ustilago maydis by Annexin V-FITC Staining.

Programmed cell death (PCD) guides the transition between key developmental stages in many organisms. PCD also remains an important fate for many organisms upon exposure to different stress conditions. Therefore, an insight into the progression of PCD during the execution of a biological phenomenon can yield significant details of the underlying mechanism. Apoptosis, as well as apoptosis-like programmed cell death, constitutes one of the forms of PCD in higher and lower eukaryotes respectively. Flipping of phosphatidylserine (PS) from the inner leaflet of the plasma membrane to the outer leaflet is among the different hallmarks of apoptosis/apoptosis-like PCD that marks the initiation of the said cell death event. This flipping can be detected through staining of the target cells using annexin V-FITC that binds specifically to PS. In Ustilago maydis the staining of the externally exposed PS by annexin V-FITC is difficult due to the presence of cell wall. The key to such staining, therefore, relies on the gentle removal of the cell wall without significantly altering the underlying plasma membrane architecture/topology. This protocol highlights the dependence of the PS staining on the extent of protoplastation of the stressed cells in Ustilago maydis.

The spectrum of myocardial homeostasis mechanisms in the settings of cardiac surgery procedures (Review).

Classic cardiac surgery, determined through the function of cardiopulmonary bypass machine and myocardial cardioplegic arrest, represents the most controlled scenario for cardiomyocyte homeostatic disturbances due to systemic inflammatory response and myocardial reperfusion injury. An increasing number of studies have demonstrated that myocardial cell homeostasis in cardiac surgery procedures is a sequence of molecularly interrelated and overlapping mechanisms in the form of apoptosis, autophagy and necrosis, which are activated by a plethora of induced inflammatory mediators and gene-related signaling pathways. In this study, we outline the molecular mechanisms of the cardiomyocyte adaptive homeostatic process and the associated clinical implications, in the settings of classic cardiac surgery procedures.

Heterologous expression of anti-apoptotic human 14-3-3β/α enhances iron-mediated programmed cell death in yeast.

The induction of Programmed Cell Death (PCD) requires the activation of complex responses involving the interplay of a variety of different cellular proteins, pathways, and processes. Uncovering the mechanisms regulating PCD requires an understanding of the different processes that both positively and negatively regulate cell death. Here we have examined the response of normal as well as PCD resistant yeast cells to different PCD inducing stresses. As expected cells expressing the pro-survival human 14-3-3β/α sequence show increased resistance to numerous stresses including copper and rapamycin. In contrast, other stresses including iron were more lethal in PCD resistant 14-3-3β/α expressing cells. The increased sensitivity to PCD was not iron and 14-3-3β/α specific since it was also observed with other stresses (hydroxyurea and zinc) and other pro-survival sequences (human TC-1 and H-ferritin). Although microscopical examination revealed little differences in morphology with iron or copper stresses, cells undergoing PCD in response to high levels of prolonged copper treatment were reduced in size. This supports the interaction some forms of PCD have with the mechanisms regulating cell growth. Analysis of iron-mediated effects in yeast mutant strains lacking key regulators suggests that a functional vacuole is required to mediate the synergistic effects of iron and 14-3-3β/α on yeast PCD. Finally, mild sub-lethal levels of copper were found to attenuate the observed inhibitory effects of iron. Taken together, we propose a model in which a subset of stresses like iron induces a complex process that requires the cross-talk of two different PCD inducing pathways.

Reovirus FAST Protein Enhances Vesicular Stomatitis Virus Oncolytic Virotherapy in Primary and Metastatic Tumor Models

The reovirus fusion-associated small transmembrane (FAST) proteins are the smallest known viral fusogens (∼100–150 amino acids) and efficiently induce cell-cell fusion and syncytium formation in multiple cell types. Syncytium formation enhances cell-cell virus transmission and may also induce immunogenic cell death, a form of apoptosis that stimulates immune recognition of tumor cells. These properties suggest that FAST proteins might serve to enhance oncolytic virotherapy. The oncolytic activity of recombinant VSVΔM51 (an interferon-sensitive vesicular stomatitis virus [VSV] mutant) encoding the p14 FAST protein (VSV-p14) was compared with a similar construct encoding GFP (VSV-GFP) in cell culture and syngeneic BALB/c tumor models. Compared with VSV-GFP, VSV-p14 exhibited increased oncolytic activity against MCF-7 and 4T1 breast cancer spheroids in culture and reduced primary 4T1 breast tumor growth in vivo. VSV-p14 prolonged survival in both primary and metastatic 4T1 breast cancer models, and in a CT26 metastatic colon cancer model. As with VSV-GFP, VSV-p14 preferentially replicated in vivo in tumors and was cleared rapidly from other sites. Furthermore, VSV-p14 increased the numbers of activated splenic CD4, CD8, natural killer (NK), and natural killer T (NKT) cells, and increased the number of activated CD4 and CD8 cells in tumors. FAST proteins may therefore provide a multi-pronged approach to improving oncolytic virotherapy via syncytium formation and enhanced immune stimulation.

Postconditioning attenuates bile duct cell damage by apoptosis from liver ischemia-reperfusion injury in rats

Objective To study the protective effect of postconditioning on bile duct cell damage in the form of apoptosis during liver ischemia-reperfusion (IR) injury by observing the expression of B cell lymphoma/leukemia-2 (bcl-2) and B cell lymphoma/leukemia-2 associated X protein (bax) on bile ducts. Methods Thirty healthy male SD rats were randomly divided into three groups: sham-operation (SO) group, IR group and ischemic postconditioning (IPO) group. IPO was achieved by 6 brief reperfused/ischemia cycles before the persistent reperfusion procedure. The samples of blood and hepatic tissue of all groups were taken after experiment. The activity of γ-glutamyl transpeptidase (GT) in serum was determined. The expression of bcl-2 and bax on bile ducts was detected by immunohistochemistry. The apoptosis index on bile ducts was observed by TdT-mediated dUTP nick end labeling (TUNEL) methods. Results The activity of γ-GT was lower in IPO group [(26.30±3.32) U/L] than that in IR group [(34.64±3.28) U/L] with the difference being statistically significant (P=0.001). As compared with the IR group, the expression of bcl-2 on bile ducts was up-regulated [(77.94±5.25)% vs. (42.67±3.73)%], and that of bax down-regulated [(70.10±4.27)% vs. (90.17±2.12)%] in IPO group, with the difference being statistically significant (P=0.000). As compared with IR group, the apoptosis index in IPO group was decreased [(58.90±2.75)% vs. (79.31±1.12)%, P=0.000], and the pathologically morphologic damages of the bile duct cells were attenuated. Conclusion In the process of liver IR, the postconditioning can promote the expression of bcl-2 and inhibit the expression of bax on bile duct, which may withstand the happening of the bile duct cell apoptosis, thus attenuating the bile duct damage caused by liver IR injury. Key words: Reperfusion injury; Postconditioning; Bile duct; Apoptosis; B cell lymphoma/leukemia-2; B cell lymphoma/leukemia-2 associated X protein

Effect of curcumol on proliferation, apoptosis and enhancer of zeste homolog 2 expression in bladder cancer EJ cells

Objective To observe the effect of curcumol on proliferation, apoptosis and enhancer of zeste homolog 2 (EZH2) expression in human bladder cancer line cell EJ, and to explore its molecular mechanism. Methods The bladder cancer EJ cells were treated with different concentrations of curcumol (12.5, 25.0, 50.0, and 100.0 mg/L) and the control group was given 1% anhydrous ethanol. The inhibitory effect of curcumol on the growth of EJ cells was evaluated by cell counting kit-8 (CCK-8) assay. Special morphological changes of apoptosis were observed by Hoechst 33258 flourescence staning. Flow cytometry technique was used to detect the apoptosis rate of each experimental group. The expression of EZH2 mRNA and protein was examined with reverse transcriptase-polymerase chain reaction (RT-PCR) and Western boltting. Results EJ cells proliferation was obviously inhibited by curcumol in a time- and concentration-dependent manner. The inhibiton rate was (32.94±0.93)%, (46.75±1.28)%, (58.16±0.76)% and (69.13±1.94)%, and the apoptosis rate was (3.60±0.46)%, (6.70±1.83)%, (16.20±1.61)% and (28.70±2.65)% in curcumol-treated (12.5, 25.0, 50.0, and 100.0 mg/L) groups respectively. A typical form of apoptosis was detected in the high concentration of curcumol by fluorescent inverted phase contrast microscope. As compared with the control group, with the increases in concentrations of curcumenol, the expression of EZH2 mRNA and protein was gradually declined. Conclusion Curcumol could significantly inhibit the growth of EJ cells and induce the apoptosis, which may be related to the down-regulation of EZH2. Key words: Curcumol; Bladder cancer; Enhancer of zeste homolog 2

When PERK inhibitors turn out to be new potent RIPK1 inhibitors: critical issues on the specificity and use of GSK2606414 and GSK2656157.

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes a state of cellular stress known as ER stress. The cells respond to ER stress by activating the unfolded protein response (UPR), a signaling network emerging from the ER-anchored receptors IRE1α, PERK and ATF6. The UPR aims at restoring ER protein-folding homeostasis, but turns into a toxic signal when the stress is too severe or prolonged. Recent studies have demonstrated links between the UPR and inflammation. Consequently, small molecule inhibitors of IRE1α and PERK have become attractive tools for the potential therapeutic manipulation of the UPR in inflammatory conditions. TNF is a master pro-inflammatory cytokine that drives inflammation either directly by promoting gene activation, or indirectly by inducing RIPK1 kinase-dependent cell death, in the form of apoptosis or necroptosis. To evaluate the potential contribution of the UPR to TNF-induced cell death, we tested the effects of two commonly used PERK inhibitors, GSK2606414 and GSK2656157. Surprisingly, we observed that both compounds completely repressed TNF-mediated RIPK1 kinase-dependent death, but found that this effect was independent of PERK inactivation. Indeed, these two compounds turned out to be direct RIPK1 inhibitors, with comparable potency to the recently developed RIPK1 inhibitor GSK'963 (about 100 times more potent than NEC-1s). Importantly, these compounds completely inhibited TNF-mediated RIPK1-dependent cell death at a concentration that did not affect PERK activity in cells. In vivo, GSK2656157 administration protected mice from lethal doses of TNF independently of PERK inhibition and as efficiently as GSK'963. Together, our results not only report on new and very potent RIPK1 inhibitors but also highlight the risk of misinterpretation when using these two PERK inhibitors in the context of ER stress, cell death and inflammation.

Non-apoptotic cell death in animal development.

Programmed cell death (PCD) is an important process in the development of multicellular organisms. Apoptosis, a form of PCD characterized morphologically by chromatin condensation, membrane blebbing, and cytoplasm compaction, and molecularly by the activation of caspase proteases, has been extensively investigated. Studies in Caenorhabditis elegans, Drosophila, mice, and the developing chick have revealed, however, that developmental PCD also occurs through other mechanisms, morphologically and molecularly distinct from apoptosis. Some non-apoptotic PCD pathways, including those regulating germ cell death in Drosophila, still appear to employ caspases. However, another prominent cell death program, linker cell-type death (LCD), is morphologically conserved, and independent of the key genes that drive apoptosis, functioning, at least in part, through the ubiquitin proteasome system. These non-apoptotic processes may serve as backup programs when caspases are inactivated or unavailable, or, more likely, as freestanding cell culling programs. Non-apoptotic PCD has been documented extensively in the developing nervous system, and during the formation of germline and somatic gonadal structures, suggesting that preservation of these mechanisms is likely under strong selective pressure. Here, we discuss our current understanding of non-apoptotic PCD in animal development, and explore possible roles for LCD and other non-apoptotic developmental pathways in vertebrates. We raise the possibility that during vertebrate development, apoptosis may not be the major PCD mechanism.

Caspase-8: not so silently deadly.

Apoptosis is a caspase-dependent programmed form of cell death, which is commonly believed to be an immunologically silent process, required for mammalian development and maintenance of cellular homoeostasis. In contrast, lytic forms of cell death, such as RIPK3- and MLKL-driven necroptosis, and caspase-1/11-dependent pyroptosis, are postulated to be inflammatory via the release of damage associated molecular patterns (DAMPs). Recently, the function of apoptotic caspase-8 has been extended to the negative regulation of necroptosis, the cleavage of inflammatory interleukin-1β (IL-1β) to its mature bioactive form, either directly or via the NLRP3 inflammasome, and the regulation of cytokine transcriptional responses. In view of these recent advances, human autoinflammatory diseases that are caused by mutations in cell death regulatory machinery are now associated with inappropriate inflammasome activation. In this review, we discuss the emerging crosstalk between cell death and innate immune cell inflammatory signalling, particularly focusing on novel non-apoptotic functions of caspase-8. We also highlight the growing number of autoinflammatory diseases that are associated with enhanced inflammasome function.

The Implications of Several Forms of Programmed Necrosis for Cancer Therapy

The dogma that apoptosis and autophagy are the sole forms of Programmed Cell Death (PCD) is no longer accepted, due to the recent discovery of programmed necrosis, a non-apoptotic, non-autophagic form of PCD. Necroptosis, parthanatos, pyroptosis, and ferroptosis are all forms of programmed necrosis, as these types of cell death dismantle the cell in an ordered fashion that is distinctly different from apoptosis or autophagy. Several key cellular mediators and events in these types of PCD have been discovered. Here, we discuss the basic characteristics, molecular pathways, and possible implications of these lesser-known types of PCD in cancer treatment modalities such as chemotherapy and radiotherapy. Because resistance to apoptosis is often responsible for cancer treatment failures, novel therapeutic strategies that can activate alternative cell death programs have great appeal. Understanding the underlying mechanisms of these types of PCD may facilitate the development of diverse therapeutic strategies, particularly against apoptosis-resistant cancers.

Dissociation of JNK Activation from Elevated Levels of Reactive Oxygen Species, Cytochrome c Release, and Cell Death in NGF-Deprived Sympathetic Neurons.

Withdrawal of nerve growth factor (NGF) from sympathetic neurons causes their apoptotic death. Activation of c-Jun NH2-terminal kinase (JNK) may contribute to this death by the induction and phosphorylation of pro-apoptotic Bcl-2 proteins, such as Bax, that are involved in cytochrome c release from mitochondria and reactive oxygen species (ROS) production. Induction of either JNK or ROS may stimulate the other, and both may regulate release of apoptogenic factors from the mitochondria. In order to discern the relationship between JNK and ROS in apoptosis, we treated NGF-deprived, mouse sympathetic neurons with a JNK inhibitor and examined the effect on several important apoptotic events. Block of JNK activation prevented induction of c-Jun expression and resulted in a dose-dependent, yet surprisingly modest, increase in cell survival after 48h of NGF deprivation. JNK suppression was also not sufficient to prevent the elevation in ROS or the release of cytochrome c from the mitochondria in NGF-deprived sympathetic neurons. Bax deletion prevents apoptotic death of NGF-deprived neurons by preventing release of cytochrome c from their mitochondria. It also prevents increased ROS on NGF deprivation. However, we found that induction of c-Jun in cells lacking Bax was equivalent to that in wild-type neurons. Our results suggest that while JNK activation plays an important role in many forms of apoptosis, it may not be a crucial regulator of Bax-dependent events involved in the apoptotic death of mouse sympathetic neurons deprived of NGF and that ROS is not involved in its activation in these cells.

Distinct cytoprotective roles of pyruvate and ATP by glucose metabolism on epithelial necroptosis and crypt proliferation in ischaemic gut.

Intestinal ischaemia causes epithelial death and crypt dysfunction, leading to barrier defects and gut bacteria-derived septic complications. Enteral glucose protects against ischaemic injury; however, the roles played by glucose metabolites such as pyruvate and ATP on epithelial death and crypt dysfunction remain elusive. A novel form of necrotic death that involves the assembly and phosphorylation of receptor interacting protein kinase 1/3 complex was found in ischaemic enterocytes. Pyruvate suppressed epithelial cell death in an ATP-independent manner and failed to maintain crypt function. Conversely, replenishment of ATP partly restored crypt proliferation but had no effect on epithelial necroptosis in ischaemic gut. Our data argue against the traditional view of ATP as the main cytoprotective factor by glucose metabolism, and indicate a novel anti-necroptotic role of glycolytic pyruvate under ischaemic stress. Mesenteric ischaemia/reperfusion induces epithelial death in both forms of apoptosis and necrosis, leading to villus denudation and gut barrier damage. It remains unclear whether programmed cell necrosis [i.e. receptor-interacting protein kinase (RIP)-dependent necroptosis] is involved in ischaemic injury. Previous studies have demonstrated that enteral glucose uptake by sodium-glucose transporter 1 ameliorated ischaemia/reperfusion-induced epithelial injury, partly via anti-apoptotic signalling and maintenance of crypt proliferation. Glucose metabolism is generally assumed to be cytoprotective; however, the roles played by glucose metabolites (e.g. pyruvate and ATP) on epithelial cell death and crypt dysfunction remain elusive. The present study aimed to investigate the cytoprotective effects exerted by distinct glycolytic metabolites in ischaemic gut. Wistar rats subjected to mesenteric ischaemia were enterally instilled glucose, pyruvate or liposomal ATP. The results showed that intestinal ischaemia caused RIP1-dependent epithelial necroptosis and villus destruction accompanied by a reduction in crypt proliferation. Enteral glucose uptake decreased epithelial cell death and increased crypt proliferation, and ameliorated mucosal histological damage. Instillation of cell-permeable pyruvate suppressed epithelial cell death in an ATP-independent manner and improved the villus morphology but failed to maintain crypt function. Conversely, the administration of liposomal ATP partly restored crypt proliferation but did not reduce epithelial necroptosis and histopathological injury. Lastly, glucose and pyruvate attenuated mucosal-to-serosal macromolecular flux and prevented enteric bacterial translocation upon blood reperfusion. In conclusion, glucose metabolites protect against ischaemic injury through distinct modes and sites, including inhibition of epithelial necroptosis by pyruvate and the promotion of crypt proliferation by ATP.

A novel method for primary neuronal culture and characterization under different high temperature.

Heatstroke is a big threat to human health; however, the characteristic of pathological changes of neurons during heatstroke development remains unclear. Here, using an in vitro model of primary cultured neurons from newborn Wistar rats, we investigated the effects of the different combinations of high temperature (37, 39, 41, 43, 45, and 47°C) and exposure time (45min and 1h) on the neurons. We found that, under the treatment of 45min-heat, the neurons could resist high temperature up to 45°C, and under the treatment of 1h-heat, the mortality of neurons increased as the temperature rises. After heating for 1h, only a small minority of the neurons died under 41 and 43°C, which primarily occurred in the form of apoptosis. Up to 45°C for 1h, most neurons occurred to necrosis. Meaningfully, some necrotic neurons expressed specific fried egg-like morphology. Our findings suggest that different high temperatures and exposure times were two key factors influencing the death of neurons. Under the high temperature (below 43°C for 1h) similar to heatstroke, it just led a small percentage of neurons to apoptosis, and anti-apoptosis controls for preventing and treating heatstroke are promising.

Poly-ubiquitination in TNFR1-mediated necroptosis.

Tumor necrosis factor (TNF) is a master pro-inflammatory cytokine, and inappropriate TNF signaling is implicated in the pathology of many inflammatory diseases. Ligation of TNF to its receptor TNFR1 induces the transient formation of a primary membrane-bound signaling complex, known as complex I, that drives expression of pro-survival genes. Defective complex I activation results in induction of cell death, in the form of apoptosis or necroptosis. This switch occurs via internalization of complex I components and assembly and activation of secondary cytoplasmic death complexes, respectively known as complex II and necrosome. In this review, we discuss the crucial regulatory functions of ubiquitination—a post-translational protein modification consisting of the covalent attachment of ubiquitin, and multiples thereof, to target proteins—to the various steps of TNFR1 signaling leading to necroptosis.

Cell death and neurodegeneration in the postnatal development of cerebellar vermis in normal and Reeler mice

Programmed cell death (PCD) was demonstrated in neurons and glia in normal brain development, plasticity, and aging, but also in neurodegeneration. (Macro)autophagy, characterized by cytoplasmic vacuolization and activation of lysosomal hydrolases, and apoptosis, typically entailing cell shrinkage, chromatin and nuclear condensation, are the two more common forms of PCD. Their underlying intracellular pathways are partly shared and neurons can die following both modalities, according to the type of death-triggering stimulus. Reelin is an extracellular protein necessary for proper neuronal migration and brain lamination. In the mutant Reeler mouse, its absence causes neuronal mispositioning, with a notable degree of cerebellar hypoplasia that was tentatively related to an increase in PCD. We have carried out an ultrastructural analysis on the occurrence and type of postnatal PCD affecting the cerebellar neurons in normal and Reeler mice. In the forming cerebellar cortex, PCD took the form of apoptosis or autophagy and mainly affected the cerebellar granule cells (CGCs). Densities of apoptotic CGCs were comparable in both mouse strains at P0-P10, while, in mutants, they increased to become significantly higher at P15. In WT mice the density of autophagic neurons did not display statistically significant differences in the time interval examined in this study, whereas it was reduced in Reeler in the P0-P10 interval, but increased at P15. Besides CGCs, the Purkinje neurons also displayed autophagic features in both WT and Reeler mice. Therefore, cerebellar neurons undergo different types of PCD and a Reelin deficiency affects the type and degree of neuronal death during postnatal development of the cerebellum.

Holding RIPK1 on the Ubiquitin Leash in TNFR1 Signaling.

The kinase RIPK1 is an essential signaling node in various innate immune signaling pathways being most extensively studied in the TNFR1 signaling pathway. TNF signaling can result in different biological outcomes including gene activation and cell death induction in the form of apoptosis or necroptosis. RIPK1 is believed to be crucial for regulating the balance between these opposing outcomes. It is therefore not surprising that RIPK1 is highly regulated, most notably by phosphorylation, ubiquitination, and their respective reversals. In this review, we discuss the biological functions of RIPK1 within the context of TNFR1 signaling. Finally, we discuss recent advances in the knowledge on three ubiquitin E3 ligases that exert regulatory functions on RIPK1 signaling: cIAP1, cIAP2, and LUBAC.

N-(3-oxo-acyl) homoserine lactone inhibits tumor growth independent of Bcl-2 proteins.

Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule for bacterial communication. C12 has also been reported to induce apoptosis in various types of tumor cells. However, the detailed molecular mechanism of C12-triggerred tumor cell apoptosis is still unclear. In addition, it is completely unknown whether C12 possesses any potential therapeutic effects in vivo. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in tumor cells through inducing mitochondrial membrane permeabilization independent of both pro- and anti-apoptotic Bcl-2 proteins. Importantly, C12 inhibits tumor growth in animals regardless of either pro- or anti-apoptotic Bcl-2 proteins. Furthermore, opposite to conventional chemotherapeutics, C12 requires paraoxonase 2 (PON2) to exert its cytotoxicity on tumor cells in vitro and its inhibitory effects on tumor growth in vivo. Overall, our results demonstrate that C12 inhibits tumor growth independent of both pro- and anti-apoptotic Bcl-2 proteins, and through inducing unique apoptotic signaling mediated by PON2 in tumor cells.

Goniothalamin induces cell cycle arrest and apoptosis in H400 human oral squamous cell carcinoma: A caspase-dependent mitochondrial-mediated pathway with downregulation of NF-κβ

Goniothalamin is a natural occurring styryl-lactone compound isolated from Goniothalamus macrophyllus. It had been demonstrated to process promising anticancer activity on various cancer cell lines. However, little study has been carried out on oral cancer. The aim of this study was to determine the cytotoxic effects of goniothalamin against H400 oral cancer cells and its underlying molecular pathways. Results from MTT assay demonstrated that goniothalamin exhibited selective cytotoxicity as well as inhibited cells growth of H400 in dose and time-dependent manner. This was achieved primarily via apoptosis where apoptotic bodies and membrane blebbing were observed using AO/PI and DAPI/Annexin V-FITC fluorescence double staining. In order to understand the apoptosis mechanisms induced by goniothalamin, apoptosis assessment based on mitochondrial membrane potential assay and cytochrome c enzyme-linked immunosorbent assay were carried out. Results demonstrated that the depolarization of mitochondrial transmembrane potential facilitated the release of mitochondrial cytochrome c into cytosol. Caspases assays revealed the activation of initiator caspase-9 and executioner caspase-3/7 in dose-dependent manners. This form of apoptosis was closely associated with the regulation on Bcl-2 family proteins, cell cycle arrest at S phase and inhibition of NF-κβ translocation from cytoplasm to nucleus. Conclusion, goniothalamin has the potential to act as an anticancer agent against human oral squamous cell carcinoma (H400 cells).

Relationship between anoikis and tumor invasion and metastasis

Anoikis, a specific form of programmed cell death, is triggered by cell detachment from extracellular matrix or adjacent cell. Studies have found that the most kinds of tumor cells had anoikis resistance characteristic, which may inhibit pro-apoptosis protein, block anoikis inside and outside pathways, up-regulate pro-survival factor signals, and promote survival, invasion and metastasis of tumor cells in the end. The review summarized the mechanism of anoikis and the relationship between anoikis and tumor invasion and the metastasis. Key words: Neoplasms; Anoikis; Neoplasm invasiveness; Neoplasm metastasis

A Conserved Core of Programmed Cell Death Indicator Genes Discriminates Developmentally and Environmentally Induced Programmed Cell Death in Plants.

A plethora of diverse programmed cell death (PCD) processes has been described in living organisms. In animals and plants, different forms of PCD play crucial roles in development, immunity, and responses to the environment. While the molecular control of some animal PCD forms such as apoptosis is known in great detail, we still know comparatively little about the regulation of the diverse types of plant PCD. In part, this deficiency in molecular understanding is caused by the lack of reliable reporters to detect PCD processes. Here, we addressed this issue by using a combination of bioinformatics approaches to identify commonly regulated genes during diverse plant PCD processes in Arabidopsis (Arabidopsis thaliana). Our results indicate that the transcriptional signatures of developmentally controlled cell death are largely distinct from the ones associated with environmentally induced cell death. Moreover, different cases of developmental PCD share a set of cell death-associated genes. Most of these genes are evolutionary conserved within the green plant lineage, arguing for an evolutionary conserved core machinery of developmental PCD. Based on this information, we established an array of specific promoter-reporter lines for developmental PCD in Arabidopsis. These PCD indicators represent a powerful resource that can be used in addition to established morphological and biochemical methods to detect and analyze PCD processes in vivo and in planta.