AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation ScienceHealth Care
Cell CycleS Phase Cell Cycle CheckpointsG2 Phase Cell Cycle CheckpointsG1 Phase Cell Cycle CheckpointsM Phase Cell Cycle CheckpointsCell Cycle ProteinsG2 PhaseCell Cycle CheckpointsDNA DamageCheckpoint Kinase 2S PhaseG1 PhaseGenes, cdcAtaxia Telangiectasia Mutated ProteinsMitosisProtein-Serine-Threonine KinasesTumor Suppressor Protein p53Protein Kinasescdc25 PhosphatasesCyclin-Dependent Kinase Inhibitor p21DNA RepairCDC2 Protein KinaseDNA-Binding ProteinsCyclinsPhosphorylationCell DivisionApoptosisTumor Suppressor ProteinsCyclin B1Cell Line, TumorDNA ReplicationGamma RaysNuclear ProteinsAtaxia TelangiectasiaHydroxyureaRadiation, IonizingCell ProliferationCyclin BSpindle ApparatusRetinoblastoma ProteinRadiation ToleranceFlow CytometryG0 PhaseCyclin-Dependent Kinase 2Signal TransductionHeLa CellsCell LineMutationCyclin-Dependent KinasesCyclin-Dependent Kinase Inhibitor p27Genomic InstabilityCyclin D1Cyclin EUltraviolet RaysSaccharomyces cerevisiae ProteinsCell SurvivalNocodazoleSaccharomyces cerevisiaeSchizosaccharomycesTumor Cells, CulturedFibroblastsSchizosaccharomyces pombe ProteinsDNA Breaks, Double-StrandedRNA, Small InterferingCyclin-Dependent Kinase 4HistonesChromosomal InstabilityBlotting, WesternModels, BiologicalAntineoplastic Agents, PhytogenicMolecular Sequence DataCells, CulturedFungal ProteinsCell NucleusBRCA1 ProteinDNAMimosineAntineoplastic AgentsAllyl CompoundsInterphaseGenes, p53CDC2-CDC28 KinasesKinetochoresAphidicolinCyclin ADose-Response Relationship, RadiationIntracellular Signaling Peptides and ProteinsTranscription FactorsGene Expression Regulation, NeoplasticMethyl MethanesulfonateDNA Repair EnzymesProtein BindingAmino Acid SequenceTime FactorsCaffeineChromatinDose-Response Relationship, DrugNucleic Acid Synthesis InhibitorsBase SequenceCarrier Proteins
MitosisProgressionKinaseProteinsInhibitorsProliferationAssembly checkpointInhibitionTumor cellsIntra-S-phaseReplicationDownstreamKnockdownCentrosome cyclePathwaysBiologyInduces apoptosisPathwayChromatinMechanismsIrradiationProteinSolid tumorsApoptosis inductionMoleculesImpairmentInhibitorEukaryoticRegulatesDependentMicrotubuleMechanismRegulationChk2CytotoxicityDamageApoptoticViabilityTransitionOverexpressionResistanceInduceInhibitsInactivationFlow cytometry analysisKinasesInduction of cell cycle arrestNude miceSignificantlySuppressionInhibitoryCancerGene-expressionEpithelialChromosomeResponseSensitivityCytokinesisHuman melanoma
Mitosis10
  • Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. (kegg.jp)
  • Similar to these drugs, eribulin is a microtubule inhibitor that induces apoptosis of cancer cells by stopping mitosis in the G2/M phase of the cell cycle . (shu.edu)
  • DSBs are first detected and signaled by the DNA damage checkpoint that triggers cell cycle arrest, providing time for the cell to repair damaged chromosomes before entering mitosis. (cea.fr)
  • Cell cycle analysis revealed arsenite-sensitive cells arrested in mitosis whereas arsenite-resistant cells did not, suggesting that induction of mitotic arrest occurs at lower intracellular arsenic concentrations. (uky.edu)
  • Inhibiting WEE1 abrogates G2 cell cycle arrest, resulting The tyrosine kinase WEE1 regulates cyclin-dependent kinase in premature entry into mitosis and leading to aberrantly 1 (CDK1), which drives cells from the G2 phase into mitosis, high CDK2 activity in S-phase cells, with the deregulated and CDK2, which drives cells into and through the S phase DNA replication resulting in replication stress [1, 5]. (sagepub.com)
  • Polo-like kinases (Plks) a family group of 5 crucial serine/threonine kinases (Plk1-Plk5) involved with cell division and mitosis represent a promising target. (researchensemble.com)
  • Required in higher cells for entry into S-phase and mitosis. (arigobio.cn)
  • During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation. (arigobio.cn)
  • Here, we challenge this view and show that HPV-18 E2 over-activates the Spindle Assembly Checkpoint (SAC) and induces DNA breaks in mitosis followed by aneuploidy. (docksci.com)
  • Required for normal cell cycle progression from G2 to mitosis. (helixlabs.ai)
Progression8
  • CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. (kegg.jp)
  • Paradoxically, progression deeper into cell cycle arrest was accompanied by increases in proliferative effectors such as CDKs and cyclins, which can drive cell cycle re-entry by overcoming p21 induction. (bvsalud.org)
  • In the presence of errors or damage during DNA replication, cell cycle checkpoint nodes and repair machinery work in concert to retard cell cycle progression until sufficient repair has been achieved. (bmj.com)
  • 12 The activation of cyclin/CDK complex accelerates cell cycle progression, which are regulated by phosphorylation. (jcpjournal.org)
  • PIG3 knockdown led to an abnormal DNA damage response, including decreased IR-induced phosphorylation of H2AX, Chk1, Chk2 and Kap-1 as well as a prolonged G2-M arrest and aberrant mitotic progression. (ijbs.com)
  • Treatment effects were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, western blot, cell viability, and cell cycle progression. (nih.gov)
  • Thus, WEE1 inhibition sensitizes cancers have loss-of-function TP53 mutations, meaning that tumor cells to DNA-damaging chemotherapy and can lead to they become more dependent on the G2/M- and S-phase unstable DNA replication, DNA damage and mitotic catas- checkpoints to halt progression of the cell cycle [3, 4]. (sagepub.com)
  • Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression. (arigobio.cn)
Kinase12
  • Cell-cycle arrest was associated with the engagement of checkpoint kinase 2-cell division cycle 25C-cyclin-dependent kinase 1/cyclin B1 signaling. (bioone.org)
  • In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. (kegg.jp)
  • The WEE-1 kinase is a key regulator of several cell cycle checkpoints including G2/M. WEE-1 inhibition can force cells in a state of arrest to continue the cell cycle, ultimately leading to cell death. (almacgroup.com)
  • Tel1p, the yeast ATM-like checkpoint kinase, was highly enriched at short telomeres from early S through G2 phase and even into the next cell cycle. (princeton.edu)
  • The presence of replication stress activates the DNA damage response and downstream checkpoint proteins including ataxia telangiectasia and Rad3 related kinase (ATR), checkpoint kinase 1 (CHK1), and WEE1-like protein kinase (WEE1), which trigger cell cycle arrest while protecting and restoring stalled replication forks. (bmj.com)
  • EESR induced cell cycle arrest at G2/M phase in a dose-dependent manner by modulating cyclin B, cyclin-dependent kinase 1 (CDK1), and CDK inhibitor p21 expression. (jcpjournal.org)
  • 8 , 9 Cell cycle program is regulated by cyclin/cyclin-dependent kinase (CDK) complexes. (jcpjournal.org)
  • Ectopic kinase overexpression in any culture cell line leads to polyploidy and centrosome amplification. (lookformedical.com)
  • Those transformed cells form tumours when implanted in immunodeficient mice, indicating that the kinase is an oncogene. (lookformedical.com)
  • Long term and extreme ER tension induced -cell apoptosis is certainly connected with c-jun N-terminal kinase (JNK) activation [9], [15]. (cgp60474.com)
  • Cdk1 (cyclin-dependent kinase 1), also known as p34Cdc2 (cell division control protein kinase 2) depends on cyclin A and B and is triggered by a positive feedback loop at the end of G2 phase, which is the key event that initiates mitotic entry. (arigobio.cn)
  • Cyclin-dependent kinase 2 (CDK2), a member of Cyclin-dependent kinases (CDKs), plays an important role in cell division and DNA replication. (mdpi.com)
Proteins10
  • We combined time-lapse microscopy, highly multiplexed single-cell imaging of 48 core cell cycle proteins, and manifold learning to render a visualization of the human cell cycle. (bvsalud.org)
  • Each origin is initiated by a combination of regulatory proteins that prepare the chromatin for replication before synthesis (S)-phase entry. (bmj.com)
  • Any obstacles encountered by cells in this process can lead to 'replicative stress' ( Figure 1 ), 1 which may be overcome by replicative stress response proteins, but deficiencies in this response result in accumulated errors in DNA replication and loss of genomic integrity, which lead to cell death. (bmj.com)
  • Thus, baicalein modulates the expression of DNA damage response proteins and G2/M phase regulatory molecules. (tku.edu.tw)
  • Indeed in S and G2 phase, RPA binding to 3' single strand overhangs facilitates the recruitment of proteins of the Rad52 epistasis group, among which Rad51, which carries out the strand-exchange reaction. (cea.fr)
  • It seems now clear that posttranslational modification of both DNA repair and checkpoint proteins is of importance for the regulation of their activities but how these modifications are regulated and how they affect the activity of the proteins only begins to be described. (cea.fr)
  • The expression of pro-apoptotic proteins and anti-apoptotic proteins in MCF-7 and MDA-MB-231 cells was investigated by Western blotting. (researchsquare.com)
  • ATF4 activates the transcription of C/EBP homologous proteins (CHOP), considered to mediate palmitate-induced -cell loss of life [10], [11]. (cgp60474.com)
  • In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. (arigobio.cn)
  • This phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. (docksci.com)
Inhibitors9
  • Immunotherapy mainly includes immune checkpoint inhibitors (ICIs), such as inhibitors of PD-1 (programmed cell death 1)/programmed cell death ligand 1 (PD-L1). (nature.com)
  • Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. (kegg.jp)
  • Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.org)
  • Currently one of three WEE1 inhibitors in clinical development, the Debio 0123 program was initiated based on the deepened understanding of the DNA damage response (DDR) of cancer cells. (almacgroup.com)
  • The DNA in cancer cells can be damaged by a variety of treatments such as radiation, antimetabolites, alkylating agents, DNA topoisomerase inhibitors and platinum-based chemotherapy. (almacgroup.com)
  • Small molecule inhibitors designed to target the DNA damage sensors, such as inhibitors of ataxia telangiectasia-mutated (ATM), ATR, CHK1 and WEE1, impair smooth cell cycle modulation and disrupt efficient DNA repair, or a combination of the above, have demonstrated interesting monotherapy and combinatorial activity, including the potential to reverse drug resistance and have entered developmental pipelines. (bmj.com)
  • 13 So, in one,25D resistant 40AF cells HPK1 doesn't seem inhibitor checkpoint inhibitors to signal differentiation with the JNK pathway. (cox2-inhibitors.com)
  • Blockade of CHK2 activation by CHK2 inhibitors protects cells from baicalein-mediated G2/M cell cycle arrest. (tku.edu.tw)
  • Inducing cell cycle arrest by cucurbitacins has been B7-2/CD86 Inhibitors targets properly Methyl-PEG3-Ald custom synthesis established while the detailed mechanisms and pathways are largely to become clear. (achrinhibitor.com)
Proliferation18
  • Taken together, our results suggested that decreased LAPTM5 inhibited proliferation and viability, as well as induced G0/G1 cell cycle arrest possibly via deactivation of ERK1/2 and p38 in BCa cells. (spandidos-publications.com)
  • Furthermore, previous studies suggested that knockdown of LAPTM4B , another important subtype of the LAPTM family inhibited proliferation of hepatocellular carcinoma ( 11 ), prostate ( 12 ) and breast cancer cells ( 13 ). (spandidos-publications.com)
  • JAM3 knockdown additionally inhibited trophoblast proliferation and increased the number of trophoblasts in the sub-G1 and G2/M phases, indicating cell-cycle disturbance and apoptosis. (bioone.org)
  • Exposure to benzo(a)pyrene affected the expression of genes that are involved in cell cycle regulation in both genotypes, indicating that the presence of unrepaired DNA damage in testis blocks cell proliferation to protect DNA integrity in both DNA repair proficient and deficient animals. (maastrichtuniversity.nl)
  • Binding of one molecule of eribulin to two microtubules can inhibit cell proliferation by 50%, and such binding is reversible. (shu.edu)
  • We used a siRNA strategy to reduce HSPB1 levels and showed increased intolerance to hyperthermia via reduced cell viability and/or proliferation of cells. (oncotarget.com)
  • Inhibitory effect of EESR on cancer cell growth and proliferation was determined by water-soluble tetrazolium salt assay. (jcpjournal.org)
  • EESR possessing antioxidant activity efficiently inhibits proliferation of HT29 cells by inducing both cell cycle arrest and apoptosis. (jcpjournal.org)
  • 6 , 7 Therefore, the inhibition of cancer cell proliferation by inducing cell cycle arrest and apoptosis is being an important preventive strategy against cancer. (jcpjournal.org)
  • 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-test was used to observe the proliferation of human breast cancer MCF-7 and MDA-MB-231 cells induced on VALD-3. (researchsquare.com)
  • Related to its effect on other reported cancer cells, Cuc B could considerably inhibit A549 cells proliferation and development inside a dose- and time- dependent manner. (achrinhibitor.com)
  • Although low concentrations of Cuc B showed no important impact on A549 cell proliferation right after 24 h therapy, prolonged treatment significantly inhibited cancer cells proliferation and colony formation clearly demonstrating that Cuc B is often a potent cytotoxic compound. (achrinhibitor.com)
  • The current study demonstrated that PD markedly inhibited PAC cell proliferation and triggered their apoptosis. (biomedcentral.com)
  • It is regarded as a desired target to treat cancer and tumor by interrupting aberrant cell proliferation. (mdpi.com)
  • Under experimental normoxic condition (21 % O 2 ), deferasirox (DFX) used at 10 μM for 3 days reduced proliferation, led cell cycle arrest in S and G2-M phases and induced cytotoxicity and apoptosis in U251 and U87 GBM cells. (biomedcentral.com)
  • Irradiation at a dose of 16 Gy repressed proliferation, cytotoxicity and apoptosis, but only in U251 cells, while no synergy with DFX was observed in either cell line. (biomedcentral.com)
  • The anticancer activities of iron depletion are based on the fact that neoplastic cells require more iron than normal cells for proliferation [ 2 ]. (biomedcentral.com)
  • The most significant pathways and BPs that were deregulated in the primary disease condition were associated with the cell cycle and fibroblast proliferation procedures. (genominfo.org)
Assembly checkpoint1
  • Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy. (docksci.com)
Inhibition6
  • We concluded that hyperthermia combined with silencing of HSPB1 enhanced cell death and resulted in failure to thrive in melanoma cell lines, implying the potential clinical utility of hyperthermia in combination with HSPB1 inhibition in cancer treatment. (oncotarget.com)
  • The pan caspase inhibitor Q VD OPh even more enhances DCS induced differentiation of 40AF cells by inhibition of HPK1 cleavage. (cox2-inhibitors.com)
  • To examine the mechanism by which DCS reverses resistance of 40AF buy Roscovitine cells to 1,25D, we asked if HPK1 sig naling is enhanced from the inhibition of its proteolytic cleavage, regarded to take area in other methods. (cox2-inhibitors.com)
  • Here, the results show that baicalein (5,6,7-trihydroxyflavone) treatment inhibits the growth of highly invasive ovarian cancer cells, and that baicalein-induced growth inhibition is mediated by the cell cycle arrest in the G2/M phase. (tku.edu.tw)
  • Inhibition of glutathione synthesis, glutathione S-transferase (GST) activity, and multidrug resistance protein (MRP) transporter function attenuated arsenite resistance, consistent with studies suggesting that arsenite is extruded from the cell as a glutathione conjugate by MRP-1. (uky.edu)
  • The tumor suppressor protein p53 is inhibition also exploits the G1 checkpoint deficiency seen involved in regulation of the G1 checkpoint. (sagepub.com)
Tumor cells5
  • In addition, tumor-associated antigens (TAAs) produced by irradiated tumor cells can be captured by antigen-presenting cells (APCs) in the TME and presented to T cells. (nature.com)
  • The main goal of RT consists in delivering a precise dose of radiation in a target volume, such as tumor, promoting the tumor cells eradication with as minimal damage as possible in surrounding normal tissues ( 13 ). (frontiersin.org)
  • 5) increasing the intrinsic radioresistance of normal cells through ketone bodies but decreasing that of tumor cells by targeting glycolysis. (springer.com)
  • Mechanistic investigations demonstrated the key role of the identified genes in the balance between death and survival of tumor cells. (biomedcentral.com)
  • As dependence on iron is a key feature of tumor cells, using chelators to reduce iron represents an opportunity to improve conventional GBM therapies. (biomedcentral.com)
Intra-S-phase2
  • ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. (kegg.jp)
  • PIG3 knockdown can suppress intra-S phase and G2/M checkpoints ( 8 ). (ijbs.com)
Replication4
  • Maintaining genomic integrity is of utmost importance to eukaryotic cells, which have evolved sophisticated mechanisms to ensure speed, accuracy, and an adequate pool of nucleotide and replication factors as well as high-fidelity repair pathways to correct errors occurring during DNA replication. (bmj.com)
  • Resection is accompanied by the binding of replication protein A (RPA) to the 3' single-stranded overhangs, which helps recruiting the checkpoint complexes. (cea.fr)
  • Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair. (arigobio.cn)
  • Histone synthesis is tightly coupled to DNA replication and peaks during the G1/S phase transition to account for doubling the genome. (biomedcentral.com)
Downstream5
  • Once recruited to DSB, these complexes get activated and induce the phosphorylation of numerous targets including transducing kinases, which subsequently phosphorylate downstream effectors to delay cell cycle and promote DNA repair. (cea.fr)
  • VALD-3 also regulated the Wnt/β-catenin signaling pathway in breast cancer cells, inhibiting the activation of downstream molecules. (researchsquare.com)
  • Previous data suggested that Cuc B triggered cell cycle arrest by blocking the STAT3 signaling pathway, which resulted in reduced expression of downstream targets, like Cyclin B1, Cyclin A [402]. (achrinhibitor.com)
  • Activation of STAT3 signaling could up-regulate Cyclin B1, c-Myc, Bcl-x and regulating cell growth and survival.Chk1 knockdown reversed Cuc B induced G2/M phase arrestTo dissect the downstream effector in Cuc B mediated G2/M phase arrest, the part of Chk1 was examined with Chk1 siRNA. (achrinhibitor.com)
  • Additionally, Cuc B brought on phosphorylation of your Chk1 downstream effector Cdc25C on Ser-216 and Cdk1 on Tyr15 had been also inhibited (Fig. 5C).Cuc B induced ROS generation and didn't influence STAT3 phosphorylationRecent research have shown that Cuc B induced intracellular ROS formation in HeLa, SW480, and B16F10 cells [14,15,39]. (achrinhibitor.com)
Knockdown2
  • Furthermore, we established a BCa cell model with downregulated LAPTM5, revealing a significantly delayed growth rate in the BCa cells with knockdown of LAPTM5. (spandidos-publications.com)
  • We therefore asked what role JMJD1B plays in newly synthesized histone maturation by exploiting the knockdown of JMJD1B by treating HeLa cells with siRNA against JMJD1B (siJMJD1B) and observed the reduction of both JMJD1B protein on cytosolic extracts (Fig. 1 b) and mRNA levels (Fig. 1 c) 72 h after the treatment. (biomedcentral.com)
Centrosome cycle1
  • The centrosome cycle (1 or 2 MTOC indicates microtubule organizing centers) is shown to be coordinated with the DNA/chromosome cycle (2N or 4N DNA content). (shu.edu)
Pathways7
  • Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. (kegg.jp)
  • The mechanisms of radioresistance are still poorly understood, despite it has been suggested that miRNAs play an important role in cell signaling pathways. (frontiersin.org)
  • Indeed, it has been shown that miRNAs play an important role in gene expression, mainly when associated with the monitoring of several cell and metabolic pathways, being also an essential component of the gene silencing machinery in most eukaryotic organisms ( 4 , 8 ). (frontiersin.org)
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
  • LY2157299 enhances anti-tumor effect by disrupting TGF-β-dependent HIF-1α signaling and by activating both Smad and PI3K-AKT pathways towards transcription of S/G2 checkpoints. (nih.gov)
  • Additional examination of GC16 and GC19 exposed en richment for more pathways broadly linked with cancer and EMT, the majority of which overlap or crosstalk with TNF, MAPK, or EGFR signaling. (pka-signal.com)
  • GC16 is enriched for your cytokines and inflammatory response and interleukin one processing pathways, when GC19 is enriched for T cell receptor signaling. (pka-signal.com)
Biology1
  • Understanding the organization of the cell cycle has been a longstanding goal in cell biology. (bvsalud.org)
Induces apoptosis2
  • Furthermore, T44Bf selectively induces apoptosis in leukemia cell lines when compared to normal peripheral blood mononuclear cells. (tmu.edu.tw)
  • This study is the first to show that VALD-3 induces apoptosis and cell cycle arrest in human breast cancer cells by suppressing Wnt/β-catenin signaling, indicating that it could be a potential drug for the treatment of breast cancer. (researchsquare.com)
Pathway3
  • Additionally, PIG3 mediates cancer cell death through the GPx3 pathway, and knocking down PIG3 or blocking the interaction between PIG3 and GPx3 would abolish the increase in ROS and apoptosis ( 5 ). (ijbs.com)
  • In general, NHEJ is the preferred pathway in the G1 phase of the cell cycle, while HR is favored in S and G2 phases. (cea.fr)
  • Furthermore, LY2835219 has additional anti-proliferative effects on cell cycling, including induction of an RB-associated G (1) arrest via suppression of cyclin D-CDK4/6-Rb pathway. (nih.gov)
Chromatin3
  • However, the level in which these B[a]P regulated genes are expressed differs between Wt and Xpc-/- mice (p = 0.000000141), and were predominantly involved in the regulation of cell cycle, translation, chromatin structure and spermatogenesis, indicating a general stress response. (maastrichtuniversity.nl)
  • Additionally, the checkpoint kinases modify the chromatin surrounding DNA damages through phosphorylation of the H2A histone (H2AX in mammals). (cea.fr)
  • Maintaining a proper supply of soluble histones throughout the cell cycle is important to ensure chromatin and genome stability. (biomedcentral.com)
Mechanisms4
  • RT can directly induce cancer cell death through various mechanisms, such as apoptosis, necrosis, and autophagy. (nature.com)
  • In the investigation of underlying mechanisms, we found knock down of HSPB1 further increased the proportion of apoptotic cells in hyperthermic treated melanoma cells when compared with either single agent alone, and both agents leaded to cell cycle arrest at G0/G1 or G2/M phases. (oncotarget.com)
  • Hyperthermia alone as a cancer treatment can selectively eliminate cancer cells by facilitating molecular mechanisms such as cell cycle arrest, apoptosis, necrosis and autophagy [ 4 - 6 ], or activate NK cells or DCs which in turn stimulates anti-cancer immune responses [ 7 , 8 ]. (oncotarget.com)
  • In this study, we investigated the cytotoxic and apoptotic effects of VALD-3, a Schiff base ligand synthesized from o-vanillin derivatives, on human breast cancer cells and the possible underlying mechanisms. (researchsquare.com)
Irradiation2
  • J-H Lee et al extensively investigated the participation of PIG3 in DNA damage checkpoints after UV irradiation or after treatment using the radiomimetic drug neocarzinostatin (NCS) ( 8 ). (ijbs.com)
  • Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. (helixlabs.ai)
Protein6
  • Our transcriptome analysis revealed in bladder cancer (BCa) tissues a significant induction of lysosomal-associated multispanning membrane protein 5 (LAPTM5), a lysosomal membrane protein preferentially expressing in immune cells and hematopoietic cells. (spandidos-publications.com)
  • LAPMT5 is a lysosomal membrane protein preferentially expressed in immune cells ( 5 , 6 ) and hematopoietic cells ( 7 ), having a close interaction with the Nedd4 ( 8 ), a member of the E3 ubiquitin ligases family ( 8 ). (spandidos-publications.com)
  • In addition HIV-1 Vpr protein alters the cell-cycle regulation by hijacking centrosome functions. (biomedcentral.com)
  • However, a compensatory feedback of increased mRNA expression of DNA-PKcs was formed in PIG3-depleted cells after a few passages or cell cycles of subculture, which led the recovery of the DNA-PKcs protein level and the consequent recovered efficiency of the DNA damage response. (ijbs.com)
  • The lack of arsenite-induced mitotic arrest in resistant cell lines was associated with a weakened spindle checkpoint resulting from reduced expression of spindle checkpoint protein BUBR1. (uky.edu)
  • Mammalian aurora-A belongs to a multigenic family of mitotic serine/threonine kinases comprising two other members: aurora-B and aurora-C. In this review we will focus on aurora-A that starts to localize to centrosomes only in S phase as soon as centrioles have been duplicated, the protein is then degraded in early G1. (lookformedical.com)
Solid tumors3
  • These data suggest that arsenite has potential for treatment of solid tumors but a functional spindle checkpoint is a prerequisite for a positive response to its clinical application. (uky.edu)
  • Objective This open-label Phase Ib study (NCT02341456) investigated the safety, pharmacokinetics, and clinical activity of adavosertib in combination with carboplatin alone or paclitaxel plus carboplatin in Asian patients with advanced solid tumors and defined the recommended Phase II dose. (sagepub.com)
  • administered in combination with cisplatin, carboplatin, or gemcitabine in patients with advanced solid tumors in a * Yung-Jue Bang [email protected] Phase I study (NCT00648648, PN001) [6]. (sagepub.com)
Apoptosis induction3
  • An early apoptosis induction in HepG2 cells was observed by annexin V assay, which clearly exhibited significantly increased early and late apoptosis phases both at 24 and 48 h. (phcogj.com)
  • A significantly increasing pattern of hypodiploid phases of cells also been observed, which confirm the apoptosis induction again. (phcogj.com)
  • β-peltatin initially arrested PAC cells at G2/M phase, followed by apoptosis induction. (biomedcentral.com)
Molecules2
  • In this review, we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of RT. (nature.com)
  • 10 , 11 The major molecules responsible for G2/M transition are cyclin A /CDK1 and cyclin B/CDK1. (jcpjournal.org)
Impairment2
  • The resulting impairment of the G2-M checkpoint would prevent cancer cells from repairing induced DNA damage, considerably enhancing the effect of the DNA damaging therapy and thus optimizing the therapeutic outcome. (almacgroup.com)
  • Impairment of a cell cycle checkpoint is often associated with sensitivity to chemotherapeutic drugs. (bmj.com)
Inhibitor4
  • 13 The expression of CDK inhibitor p21 is upregulated by activated p53, resulting in the suppression of G2/M transition by the inactivation of cyclin/CDK complex. (jcpjournal.org)
  • In this study, cultured human temozolomide resistance GB (43RG) cells were introduced to the MGMT inhibitor O 6 -benzylguanine combined with temozolomide and either LY2835219 (CDK 4/6 inhibitor) or LY2157299 (TGF-βRI inhibitor) seeking to overcome GB treatment resistance. (nih.gov)
  • This study establishes the groundwork for the development of a combinatorial pharmacologic approach by using either LY2385219 or LY2157299 inhibitor plus O 6 -Benzylguanine to augment temozolomide response in temozolomide-resistant GB cells. (nih.gov)
  • Precis: Pulsed high doses versus sustained low doses of the p53-MDM2 inhibitor HDM201 elicit a pro-apoptotic response from wild-type p53 cancer cells, offering guidance to current clinical trials with this and other drugs that exploit the activity of p53. (bace-signal.com)
Eukaryotic1
  • During the last decade, the non-random spatial arrangement of the genome into the nucleus of eukaryotic cells, as emerged as a key regulator of genome functions and notably of the propagation of a stable genome. (cea.fr)
Regulates2
  • promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. (arigobio.cn)
  • Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. (helixlabs.ai)
Dependent5
  • In addition, analysis of cell cycle phase dependent gene expression revealed that expression of genes involved in G1-S and G2-M phase arrest was increased after B[a]P exposure in both genotypes. (maastrichtuniversity.nl)
  • EESR showed significant antioxidant activity and inhibitory effect on HT29 cell growth in a dose-dependent manner. (jcpjournal.org)
  • Examination of cell cycle parameters showed that the DCS induced block from the G1 phase and decreased occu pancy of your G2 compartment is dependent on optimum levels of HPK1, as siHPK1 abrogated these results. (cox2-inhibitors.com)
  • In SW480 cells, Cuc B induced G2 arrest and apoptosis by means of a STAT3-independent but ROS-dependent mechanism [14]. (achrinhibitor.com)
  • Within this study, we showed that Cuc B induced G2/M arrest inside a ROS dependent manner without having affecting STAT3 in A549 cells: Cuc B induced ROSmediated DNA harm, which activated G2/M phase checkpoint through ATM-activated Chk1-Cdc25C-Cdk1 and -p53-14-3-3-s cascades. (achrinhibitor.com)
Microtubule4
  • This illustration shows the proposed relative location of the 2 known cell cycle arrest points in cells with MTD (microtubule damage). (shu.edu)
  • G1MTC, G1 phase microtubule checkpoint. (shu.edu)
  • Centrosomes are the major microtubule organizing structures in vertebrate cells. (biomedcentral.com)
  • In animal cells, centrosomes represent the major microtubule-organizing structures (MTOC). (biomedcentral.com)
Mechanism5
  • Eribulin exerts its effects via a tubulin-based antimitotic mechanism leading to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. (shu.edu)
  • Centrosome duplication is tightly regulated and limited at once per cell cycle through a mechanism that prevents re-duplication. (biomedcentral.com)
  • The objective of this study is to evaluate the antioxidant and anticancer effects of ethanol extract of S. rufopilosa (EESR) and to determine the molecular mechanism of its anticancer activity in human colon carcinoma HT29 cells. (jcpjournal.org)
  • To investigate the mechanism of EESR-mediated cytotoxicity, HT29 cells were treated with various concentrations of EESR and the induction of cell cycle arrest and apoptosis was analyzed by flow cytometry, 4,6-diamidino-2-phenylindole staining, and Western blot analysis. (jcpjournal.org)
  • In the present study, the potential mechanism of PIG3 participation in the DNA damage response induced by ionizing radiation (IR) was investigated in multiple cell lines with depleted expression of PIG3 transiently or stably by the small interference RNA and lentivirus-mediated shRNA expression strategies. (ijbs.com)
Regulation2
  • Moreover, some studies demonstrated that LAPTM5 was highly expressed in malignant B lymphomas and involved in B cell malignancies ( 10 ), involving in negative regulation of cell surface T and B cell receptor by promoting lysosome degradation ( 6 ). (spandidos-publications.com)
  • As main findings, 23 miRNAs were already identified as being involved in genetic regulation of PCa cell response to RT. (frontiersin.org)
Chk25
  • Whereas damage signals of cells activate p53 via CHK2 to repair damaged DNA, leading to cell cycle arrest. (jcpjournal.org)
  • Baicalein Induces G2/M Cell Cycle Arrest Associated with ROS Generation and CHK2 Activation in Highly Invasive Human Ovarian Cancer Cells. (tku.edu.tw)
  • Dysfunctional CHK2 impairs DNA damage-induced checkpoints, reduces apoptosis, and confers resistance to chemotherapeutic drugs and radiation therapy in ovarian cancer cells. (tku.edu.tw)
  • Baicalein-induced G2/M phase arrest is associated with an increased reactive oxygen species (ROS) production, DNA damage, and CHK2 upregulation and activation. (tku.edu.tw)
  • All the results suggest that baicalein has another novel growth inhibitory effect on highly invasive ovarian cancer cells, which is partly related to G2/M cell cycle arrest through the ROS-mediated DNA breakage damage and CHK2 activation. (tku.edu.tw)
Cytotoxicity2
  • Deferiprone, a bidentate iron chelator, has been shown to have antiproliferative and cytotoxicity activities in neuroblastoma cell lines [ 7 ]. (biomedcentral.com)
  • We cultured 6 endometrial cancer cell lines exposed to paclitaxel, studied the cell cytotoxicity, cell cycle distribution, CHFR expression, and methylation status before and after a demethylation agent (5-aza) treatment. (bmj.com)
Damage7
  • RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. (nature.com)
  • One of the treatments applied in cancer is radiotherapy (RT), a therapeutic modality that uses ionizing radiation to induce damage in unwanted cells. (frontiersin.org)
  • When this damage occurs, the cells respond by pausing the cell cycle temporarily to allow for DNA repair, hence reducing the effectiveness of cytotoxic therapies against the cancer cells. (almacgroup.com)
  • Strategies that increase replicative stress while lowering cell cycle checkpoint thresholds may allow unrepaired DNA damage to be inappropriately carried forward in replicating cells, leading to mitotic catastrophe and cell death. (bmj.com)
  • The DNA double-strand break (DSB) is considered to be the most severe type of DNA damage induced by ionizing radiation, and this form of DNA damage must be repaired immediately to prevent cell death. (ijbs.com)
  • Following DNA damage, WEE1 inhibits CDK1, leading 1 Introduction to cell cycle arrest and allowing time for DNA repair [4]. (sagepub.com)
  • Outside S-phase a histone pool is maintained in case of unanticipated changes to histone demand, such as DNA damage [ 9 ]. (biomedcentral.com)
Apoptotic3
  • 36 This indicates that the previously documented non apoptotic func tions of caspases37 may possibly contribute towards the effects of QVD on AML cells, similar to the antitumor results of other protease inhibi tors. (cox2-inhibitors.com)
  • The cell cycle distribution was analyzed through PI staining and flow cytometry analysis, while apoptotic cells were measured by double staining with Annexin V-FITC and PI. (biomedcentral.com)
  • Continuous exposure of HDM201 led to induction of p21 and delayed accumulation of apoptotic cells. (bace-signal.com)
Viability1
Transition1
  • This data-driven approach revealed the comprehensive "structure" of the cell cycle: a continuum of molecular states that cells occupy as they transition from one cell division to the next, or as they enter or exit cell cycle arrest. (bvsalud.org)
Overexpression3
  • Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION. (lookformedical.com)
  • However, overexpression of aurora-A in particular cell lines such as NIH3T3 is sufficient to induce growth on soft agar. (lookformedical.com)
  • Although, their part in EMT remains unclear, overexpression of ei ther ARRB1 or ARRB2 in HeLa cells inhibits NF B medi ated transcription. (pka-signal.com)
Resistance6
  • cleaved fragment of HPK1, amongst parental one,25D sensitive HL60 cells as well as the 40AF cells with acquired resistance to 1,25D, is shown in Figure 5C. (cox2-inhibitors.com)
  • KG 1a cells with innate resistance to 1,25D also express HPK1 C fragments, that are diminished by treatment method DCS. (cox2-inhibitors.com)
  • Vitamin D resistance of KG 1a, AML M1 type cells,39 may also be attenuated by treatment with DCS, and, as in adaptively resistant 40AF cells, this is certainly associated with all the disappearance of your cleaved fragment and concurrent improve inside the level of your FL HPK1. (cox2-inhibitors.com)
  • ICP-MS analysis indicated that arsenite-resistant SK-Mel-28 cells did not accumulate less arsenic than arsenite-sensitive A375 cells, suggesting that resistance was not attributable to reduced arsenic accumulation but rather to intrinsic properties of resistant cell lines. (uky.edu)
  • Notably, surgical treatment has also the potential advantage of removing chemoradioresistant residual tumor foci, with a higher local control and possibly better survival, since resistance of cancer cells to CRT remains a major therapeutic drawback. (biomedcentral.com)
  • In addition, cells with CHFR demethylation resulted in G2/M phase arrest that induced to paclitaxel resistance. (bmj.com)
Induce2
  • The current study found that ST has the capacity to induce cell toxicity in human liver cells. (phcogj.com)
  • Finally, JNK3 shRNA expressing INS1 cells didn't induce apoptosis in comparison to nonsense shRNA expressing INS1 cells when subjected to palmitate and high blood sugar but showed elevated caspase 9 and 3 cleavage connected with elevated and mRNA appearance. (cgp60474.com)
Inhibits1
  • Eribulin inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates. (shu.edu)
Inactivation2
Flow cytometry analysis2
Kinases2
  • Change in localisation depends on the checkpoint kinases Tel1ATM and Mec1ATR and has a positive effect on spontaneous recombination. (cea.fr)
  • History Polo-like kinases (Plks) control multiple steps during the cell cycle and Plk1 is overexpressed in urothelial cancer (UC). (researchensemble.com)
Induction of cell cycle arrest1
  • In some p53 mutants, induction of cell cycle arrest, but not apoptosis was found to be associated with a lack of induction of PIG3 expression ( 2 ). (ijbs.com)
Nude mice2
  • By xenografting human breast cancer cells into nude mice, we found that VALD-3 significantly suppressed tumor cell growth while showing low toxicity against major organs. (researchsquare.com)
  • The in vivo effects of β-peltatin and podophyllotoxin were evaluated on a subcutaneously-xenografted BxPC-3 cell nude mice model. (biomedcentral.com)
Significantly1
  • Animal study confirmed that β-peltatin significantly suppressed the growth of subcutaneously-implanted BxPC-3 cell xenografts. (biomedcentral.com)
Suppression1
  • Our data suggest that CHFR suppression regulated by hypermethylation may sensitize endometrial cancer cells to paclitaxel, and CHFR may be a promising marker to predict the response of endometrial cancer to paclitaxel. (bmj.com)
Inhibitory1
  • This can be consistent with our previ ously reported observation that JNK2 action is inhibitory to differentiation of 40AF cells. (cox2-inhibitors.com)
Cancer9
  • Furthermore, inflammatory mediators released by irradiated dying cells can attract and regulate immune cells in the tumor microenvironment (TME), further killing cancer cells. (nature.com)
  • One study reported an increased survival benefit with simultaneous RT compared with sequential administration, 8 while another study found no significant difference between the two strategies, 9 possibly because simultaneous RT plus immunotherapy and the administration of an ICI before RT may kill cancer cells as well a substantial number of immune cells, leading to poor systemic response and toxic side effects. (nature.com)
  • Belfast, Northern Ireland- March 5, 2020 - Debiopharm - a Swiss biopharmaceutical company, has announced the advancement of its first-in-human, phase 1 study as patients with advanced solid tumours will be administered with cancer treatment Debio 0123 in combination with carboplatin. (almacgroup.com)
  • The abnormal cell growth is one of the critical characteristics of cancer for invasion or spreading out to other parts of the body. (jcpjournal.org)
  • Cancer cells can grow unusually via limitless number of cell division and can avoid apoptosis. (jcpjournal.org)
  • Cuc B, one of many extensively investigated cucurbitacins, lead to diverse phase cell cycle arrest in diverse cancer cells. (achrinhibitor.com)
  • The anti-proliferative effect of Cuc B on cancer cells has been reported everywhere. (achrinhibitor.com)
  • Here, we studied the correlations between the checkpoint with forkhead-associated and ring finger (CHFR) gene expression and responses to paclitaxel in endometrial cancer cells. (bmj.com)
  • Basal cell carcinoma (BCC) is a nonmelanocytic skin cancer (ie, an epithelial tumor) that arises from basal cells (ie, small, round cells found in the lower layer of the epidermis). (medscape.com)
Gene-expression1
  • A slightly higher induction of average gene expression was observed at the G2-M checkpoint in Xpc-/- mice, but this did not reach statistical significance (P=0.086). (maastrichtuniversity.nl)
Epithelial2
  • During EMT, cells will undergo transformation from epithelial phenotype to mesenchymal phenotype ( 14 ) and many characteristics of cells will change including loss of cell-cell adhesion and acquisition of aggressive and metastatic ability ( 15 ). (spandidos-publications.com)
  • Junctional adhesion molecule 3 (JAM3) is involved in epithelial cell junction, cell polarity, and motility. (bioone.org)
Chromosome1
  • Present findings indicate that T44Bf-mediated antiproliferative effects are associated with a reversible chronic mitotic arrest caused by defects in chromosome alignment, followed by induced programmed cell death. (tmu.edu.tw)
Response2
  • This approach will enable the comparison of alternative cell cycles during development, in response to environmental perturbation and in disease. (bvsalud.org)
  • A partial response occurred in 2/12 evaluable patients (16.7%) at the recommended Phase II dose. (sagepub.com)
Sensitivity3
  • Our in vitro study demonstrated that sequential treatment of O 6 -Benzylguanine with either LY2385219 or LY2157299-enhanced temozolomide enhanced sensitivity in MGMT+ 43RG cells. (nih.gov)
  • The current study examines factors influencing sensitivity to arsenic using human malignant melanoma cell lines. (uky.edu)
  • Then we found that restored expression of CHFR by demethylation decreased the sensitivity to paclitaxel in AN3CA cells. (bmj.com)
Cytokinesis2
Human melanoma1
  • In the present study, we identified HSPB1 (HSP27) is hyperthermically inducible or endogenously highly expressed in both murine and human melanoma cell lines. (oncotarget.com)