• The current study demonstrated that PD markedly inhibited PAC cell proliferation and triggered their apoptosis. (biomedcentral.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)
  • Potential synergistic effects of various combinations including these compounds were tested by measuring cancer cell proliferation and apoptosis. (frontiersin.org)
  • Cell viability, proliferation, DNA damage response and apoptosis were investigated using immunofluorescence staining and immunoblotting. (bmj.com)
  • Results Gemcitabine treatment caused DNA damage, cellular stress, inhibited proliferation and activated cell cycle check-point sensors and induced apoptosis as shown by increased expression of g-histone H2AX, p-JNK, Chk-1/Chk-2, cleaved forms of PARP and caspase-3 in the asynchronous cells in a dose dependent manner. (bmj.com)
  • As a result, the proliferation and in vitro AMH and oestrogen production of the cells were decreased at post-exposure 24h. (bmj.com)
  • In the cells synchronized at S phase gemcitabine significantly inhibited DNA synthesis and blocked their proliferation. (bmj.com)
  • However, a function for SET8 in mammalian cell proliferation has not been determined. (rupress.org)
  • We show that small interfering RNA inhibition of SET8 expression leads to decreased cell proliferation and accumulation of cells in S phase. (rupress.org)
  • 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)
  • Recent studies have revealed that AXL contributes to leukaemic phenotypes through activation of oncogenic signalling pathways that lead to increased cell migration and proliferation. (cancerindex.org)
  • New anticancer therapy strategies refer to the inhibition of CDK-cyclin complexes as an important target to prevent uncontrolled proliferation and induce apoptosis in cancer cells ( 2 ). (spandidos-publications.com)
  • Natural polyamines, putrescine, spermidine and spermine, play essential roles in the regulation of cell growth and proliferation. (spandidos-publications.com)
  • 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)
  • RNA silencing and pharmacologic inhibitors were used to evaluate the functions of CDK7/p38α/MYC/PD-L1 axis in cancer cell proliferation and antiPD-1 therapy resistance. (biomedcentral.com)
  • AP4 presumably contributes to the phenotype of cancer cells by activating or repressing genes that harbor CAGCTG elements in their promoter regions, thereby controlling processes such as proliferation, metabolism, apoptosis, epithelial-mesenchymal transition (EMT) and metastasis [ 5 ]. (biomedcentral.com)
  • Our results demonstrate that Pulsatillae chinensis and particularly its bioactive ingredient β-peltatin suppress PAC by triggering cell cycle arrest at G2/M phase and apoptosis. (biomedcentral.com)
  • The absence of microtubule attachment to kinetochores activates the spindle assembly checkpoint, causing the cell to arrest in prometaphase. (wikipedia.org)
  • We have generated model systems to explore drug resistance in ovarian cancer, which have revealed a key pathway related to the spindle assembly checkpoint underlying paclitaxel resistance in ovarian cell lines. (biomedcentral.com)
  • Previous evidence points to numerous components of the spindle assembly checkpoint and mitotic regulation playing a major role in several cancers [ 11 , 12 ]. (biomedcentral.com)
  • Lastly, through gene expression profiling we have demonstrated disruption of the spindle assembly checkpoint in the paclitaxel resistant cell lines, indicating a potential therapeutic pathway. (biomedcentral.com)
  • Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy. (docksci.com)
  • 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)
  • 12 The activation of cyclin/CDK complex accelerates cell cycle progression, which are regulated by phosphorylation. (jcpjournal.org)
  • Exposure of the cells to gemcitabine at G2/M transition abolished the progression of mitosis, caused mitotic arrest and failure to exit mitosis as evidenced by the inhibition of Cyclin B degradation and absence of de-phosphorylation of cdc-2 at Tyr 15 residue. (bmj.com)
  • Furthermore, we find that SET8 interacts with proliferating cell nuclear antigen through a conserved motif, and SET8 is required for DNA replication fork progression. (rupress.org)
  • By exogenously modulating its activity, we demonstrate that PP1α is required to maintain CHK1 in a dephosphorylated state and, more importantly, that it is responsible for the accelerated replication fork progression in Spi1/PU.1-overexpressing cells. (oncotarget.com)
  • 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)
  • Collectively, we anticipate that this method will allow high-resolution microscopic analysis of cellular processes involving cell cycle progression, such as checkpoint activation, DNA replication, and cellular division. (biomedcentral.com)
  • The molecular biology underlying renal cell carcinoma (RCC) development and progression has been a key milestone in the management of this type of tumor. (cancerindex.org)
  • This effect was most pronounced in the progression towards metaphase, too as 4-1BB Ligand Inhibitors products inside metaphase itself (video recordings of cells undergoing regular and prolonged, aberrant mitosis, see Supplemental Figure 6). (calcium-channel.com)
  • Increased levels of polyamines in cells are considered to be involved in cancer progression. (spandidos-publications.com)
  • Cell viability was determined using Cell Counting Kit-8 assay. (biomedcentral.com)
  • Western blot, comet assay, immunostaining and flow cytometry were performed to dissect the underlying mechanisms. (bvsalud.org)
  • 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)
  • Standard techniques like cell synchronization by serum starvation, flow cytometry, N-terminal or C-terminal FLAG epitope-tagged protein expression, immunofluorescence confocal microscopy, dual luciferase assay for promoter evaluation, and chromatin immunoprecipitation assay were employed during this study. (biomedcentral.com)
  • To discover this notion, we revisited the DR-GFP repair assay in HCC1937 cells and integrated a DsRed reporter which scores for NHEJ. (calcium-channel.com)
  • The experiments were repeated for three times and quantative density is indicated Lysates of HEK 293T cells transfected with the FLAG MST2 or Y81F expression plasmid were immunoprecipitated with all the anti FLAG antibody and subjected to an in vitro kinase assay employing Histone H2B as substrate in the presence of ATP. (aktinhibitor.com)
  • Cell growth assay, cell cycle analysis, FACS, JC-1 staining, annexin V staining and immunoblotting were used to study the efficacy of ST on cancer cells. (biomedcentral.com)
  • Repair kinetics of etoposide- and ionizing radiation-induced DSBs was identical in WT, MA4- and A4M-expressing cells, as revealed by flow cytometry, by immunoblot for γH2AX and by comet assay. (ibecbarcelona.eu)
  • Another standard cell biological application of nocodazole is to induce the formation of Golgi ministacks in eukaryotic cells. (wikipedia.org)
  • We found that Dusp4 loss alone is insufficient in mediating tumorigenesis, but alternatively converges with loss in Trp53 and MYC amplification to induce tumorigenesis primarily through chromosome 5 amplification, which specifically upregulates Dbf4 , a cell cycle gene that promotes cellular replication by mediating cell cycle checkpoint escape. (biomedcentral.com)
  • The current study found that ST has the capacity to induce cell toxicity in human liver cells. (phcogj.com)
  • Lentiviral vector-based dendritic cell vaccines induce protective T cell responses against viral infection and cancer in animal models. (jci.org)
  • Several alkylating agents are commonly used in chemotherapy but may induce DNA damage to cancer cells as well as normal cells. (frontiersin.org)
  • STI571 therapy of serum starved cells for 48h did not induce apoptosis. (aktinhibitor.com)
  • Inhibition of ATR in auranofin-treated cancer cells resulted in unscheduled firing of dormant DNA replication origins, abrogation of the S phase cell cycle checkpoint and extensive DNA breakage, leading to replication catastrophe and potent synergistic lethality. (bvsalud.org)
  • Both the antioxidant NAC and the DNA polymerase inhibitor aphidicolin reduced replication stress and synergistic cytotoxicity, implicating replication stress-driven catastrophic cell death resulted from collision between oxidative DNA damage and dysregulated DNA replication. (bvsalud.org)
  • Histone synthesis is tightly coupled to DNA replication and peaks during the G1/S phase transition to account for doubling the genome. (biomedcentral.com)
  • This study identifies a novel mechanism for breast tumorigenesis implicating Dusp4 loss and p53 mutations in cellular acquisition of Dbf4 upregulation as a driver of cellular replication and cell cycle checkpoint escape. (biomedcentral.com)
  • Interestingly, replication stress in Brca2-null cells activates p53 and the expression of its target genes, including senescence-inducing Ink4/Arf. (biomedcentral.com)
  • Given the previously reported role of DUSP4 as a p53 target, a potential cell cycle checkpoint, and in mediating senescence downstream of replication stress, we hypothesized that DUSP4 may be a critical oncogenic driver in breast cancer. (biomedcentral.com)
  • SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. (rupress.org)
  • We previously showed that constitutive overexpression of the oncogenic transcription factor Spi1/PU.1 leads to pre-leukemic cells that have a shortened S phase duration with an increased replication fork speed and increased mutability in the absence of DNA breaks. (oncotarget.com)
  • Orderly progressions of events in the cell division cycle are necessary to ensure the replication of DNA and cell division. (ox.ac.uk)
  • Microscopy of nocodazole-treated cells shows that they do enter mitosis but cannot form metaphase spindles because microtubules (of which the spindles are made) cannot polymerise. (wikipedia.org)
  • Prolonged arrest of cells in mitosis due to nocodazole treatment typically results in cell death by apoptosis. (wikipedia.org)
  • Essed via mitosis utilizing live-cell confocal imaging. (calcium-channel.com)
  • Within the absence of any DNA harm, we located that BRCA14P cells spent considerably a lot more time in all phases of mitosis relative to BRCA1 wild-type (Figure 5A). (calcium-channel.com)
  • Furthermore, we found that though cells complemented with wild-type BRCA1 demonstrated a baseline level of mitotic aberrations, cells expressing BRCA14P had drastically (3-fold) enhanced levels above wild-type and a trend of 30 elevated levels above vector handle (Figure 5B), suggesting that BRCA14P produces extra insult to mitosis than having no BRCA1 at all. (calcium-channel.com)
  • As evidenced by the observed raise in mitotic aberrations (rosettes and bridges), BRCA14P cells struggle through mitosis and practical experience death via mitotic catastrophe. (calcium-channel.com)
  • This shift within the excellent of DSB repair, coupled with an inadequate G2/M arrest, permits excessively damaged cells to inappropriately try mitosis, therefore facilitating chromosomal instability and resulting in mitotic catastrophe.DISCUSSIONIt was previously recommended that the radiosensitivity of BRCA1-defective cells isn't completely attributable to impaired cell cycle checkpoints [25]. (calcium-channel.com)
  • TP53 is a checkpoint molecule that maintains genomic stability, prevents cell mitosis and induces apoptosis following abnormal chromosome segregation or chemical damage to DNA sequences [ 9 , 10 ]. (biomedcentral.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)
  • AIMS: Studies in the past have shown that inhibition of the ataxia telangiectasia and Rad3-related (ATR) kinase sensitizes cancer cells to genotoxic anticancer treatments, however, clinical use of ATR inhibitors in combination with DNA damaging chemotherapy is limited due to toxicity in healthy tissues. (bvsalud.org)
  • As a key sensor in response to DNA damage, ataxia telangiectasia and rad3-related (ATR) kinase has become a potential therapeutic target as tumor cells are to rely heavily on ATR for survival. (bvsalud.org)
  • 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)
  • In response to DNA damage, a synthetic lethal relationship exists between the cell cycle checkpoint kinase MK2 and the tumor suppressor p53. (nature.com)
  • Here, we demonstrate that the S phase checkpoint protein CHK1 is maintained in a low phosphorylation state in Spi1/PU.1-overexpressing cells and provide evidence that this is not due to negative control of its primary kinase ATR. (oncotarget.com)
  • Forced expression of NBPF1 in HEK293T cells resulted in a G1 cell cycle arrest that was accompanied by upregulation of the cyclin-dependent kinase inhibitor p21 CIP1/WAF1 in a p53-dependent manner. (biomedcentral.com)
  • These paclitaxel resistant ovarian cells demonstrate: (1) Increased IC 50 for paclitaxel and docetaxel (10 to 75-fold) and cross-resistance to anthracyclines (2) Reduced cell apoptosis in the presence of paclitaxel (3) Gene depletion involving mitotic regulators BUB1 mitotic checkpoint serine/threonine kinase, cyclin BI (CCNB1), centromere protein E (CENPE), and centromere protein F (CENPF), and (4) Functional data validating gene depletion among mitotic regulators. (biomedcentral.com)
  • This gene, which encodes a member of the serine/threonine kinase family, regulates cell polarity and functions as a tumor suppressor. (cancerindex.org)
  • Purvalanol, a novel cyclin-dependent kinase inhibitor, is referred to as a strong apoptotic inducer which causes cell cycle arrest in various cancer cells such as prostate, breast and colon cancer cell lines. (spandidos-publications.com)
  • Cyclin-dependent kinases (CDKs), are members of the serine-threonine protein kinase family and are responsible for taking control of cell cycle regulation in eukaryotic cells. (spandidos-publications.com)
  • Nocodazole has been shown to decrease the oncogenic potential of cancer cells via another microtubules-independent mechanisms. (wikipedia.org)
  • We have generated paclitaxel resistant ovarian cell lines from their corresponding native cell lines to determine driver mechanisms of drug resistance using gene expression arrays. (biomedcentral.com)
  • These pre-clinical models were used to observe cytotoxicity, cell cycle modulation and changes in gene expression to examine the mechanisms driving drug resistance. (biomedcentral.com)
  • The notion could be that unique cellular mechanisms are triggered in the breast cancer cells to stimulate BRCA2 gene expression as a temporary measure to regulate the growth of the breast cancer cells. (biomedcentral.com)
  • While BRCA2 expression is involved in cell cycle checkpoints and DNA repair, the mechanisms of cell cycle-dependent regulation of BRCA2 gene expression remains elusive. (biomedcentral.com)
  • The extremely low 5-year overall survival of patients is, in part, due to pancreatic cancer cells having several mechanisms of resistance to different chemotherapeutic treatments, one of which is their capacity to efficiently repair alkylating agent-induced DNA damage. (frontiersin.org)
  • 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)
  • However, the mechanisms involved in CDK7-mediated immune evasion are unclear in non-small cell lung cancer (NSCLC). (biomedcentral.com)
  • KEY FINDINGS: Nontoxic doses of auranofin alone increased the levels of reactive oxygen species (ROS) in cancer but not noncancerous cells, resulting in oxidative DNA damage and activation of the ATR DNA damage response pathway selectively in cancer cells. (bvsalud.org)
  • Triple treatment showed synergism in terms of exhibiting anti-tumorigenic effects by activating the Hippo YAP signaling pathway in the HCT116 cell line. (frontiersin.org)
  • Therefore, compared to normal p53-proficient cells, p53-defective cells are more reliant on MK2 activity, which drives an alternative cell cycle checkpoint pathway that stabilizes the CKI inhibitors p27 Kip1 and Gadd45α in order to maintain G 1 /S and G 2 /M arrest after certain types of DNA damage 16 , 18 . (nature.com)
  • 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)
  • VALD-3 also regulated the Wnt/β-catenin signaling pathway in breast cancer cells, inhibiting the activation of downstream molecules. (researchsquare.com)
  • 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)
  • Treatment with etoposide consistently induced cell cycle arrest in S/G2/M independent of MA4/A4M expression, revealing a proper activation of the DNA damage checkpoints. (ibecbarcelona.eu)
  • 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)
  • 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)
  • 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)
  • Presented in conjunction with cells expressing a histone 2B-GFP fusion protein (H2B-GFP), we demonstrated how this method enabled chromosomal segregation errors to be tracked in cells as they progressed through cellular division that were later identified as either diploid or polyploid. (biomedcentral.com)
  • Vaccination by direct injection of lentiviral vector was more effective in sterile alpha motif and HD-domain containing protein 1-knockout (SAMHD1-knockout) mice, suggesting that lentiviral vectors containing Vpx, a lentiviral protein that increases the efficiency of dendritic cell transduction by inducing the degradation of SAMHD1, would be an effective strategy for the treatment of chronic disease in humans. (jci.org)
  • While studying the activity of BRCA2 gene promoter in breast cancer cells, we discovered that this promoter has bi-directional activity and the product of the reverse activity (a ZAR1-like protein, we named ZAR2) silences the forward promoter at the G0/G1 phase of the cell. (biomedcentral.com)
  • ST caused G0/G1 cell cycle arrest which was accompanied by a decrease in CDK4 and cyclin D1, and an increase in p21/Cip1and p27/Kip1 protein levels. (biomedcentral.com)
  • 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)
  • The co-treatment with VE-821 and cisplatin significantly reduced cell viability and proliferative capacity compared with cisplatin mono-treatment (P (bvsalud.org)
  • The currently used diagnostic test for FA relies on the increased chromosomal breakage and radial formation of FA cells in response to diepoxybutane (DEB) compared with cells from healthy control subjects, 15 , 16 or from patients with other chromosomal instability disorders 17 or genetic syndromes. (ashpublications.org)
  • The precise regulation of the levels of cyclin proteins is fundamental to coordinate cell division with checkpoints, avoiding genome instability. (ox.ac.uk)
  • Here, we tested whether ALKBH6 plays a significant role in preventing alkylating DNA damage and decreasing genomic instability in pancreatic cancer cells. (frontiersin.org)
  • Genomic instability caused by mutation of the checkpoint molecule TP53 may endow cancer cells with the ability to undergo genomic evolution to survive stress and treatment. (biomedcentral.com)
  • In culture, cells from affected individuals exhibit elevated rates of chromosomal breakage or instability, leading to chromosomal rearrangements. (medscape.com)
  • Inactivation of AP4 in CRC cell lines resulted in increased spontaneous and c-MYC-induced DNA damage, chromosomal instability (CIN) and cellular senescence. (biomedcentral.com)
  • 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)
  • We investigated by real-time quantitative RT-PCR the expression profile of a panel of genes important in cell cycle regulation. (biomedcentral.com)
  • The construction of this cell line is the first promising step in the regulation of GAL secretion from hTERT-immortalized BMSCs, and the potential application of this system may provide a stem cell-based research platform for pain. (hindawi.com)
  • Several genes of the C-type lectin superfamily, including the rodent NKRP1 family of glycoproteins, are expressed by NK cells and may be involved in the regulation of NK cell function. (thermofisher.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)
  • Because BRCA mutations are observed in fewer than 10% of cancer patients (cBioPortal: 6.7%) 11 , 12 , 13 the identification of additional genes that share synthetic lethal sensitivity relationships with mutated oncogenes or tumor suppressors would greatly enhance the implementation of tumor cell-specific synthetic lethal sensitivity to improve an anticancer therapeutic response. (nature.com)
  • DUSP4 alterations lead to hyperactivation of MAPK signaling in many cancers, including breast cancer, which often harbor mutations in cell cycle checkpoint genes, particularly in TP53. (biomedcentral.com)
  • SL originally described a relationship between two genes, where alteration of either gene alone results in viable cells, but alteration (mutation, loss, or inhibition) of both genes simultaneously was lethal. (nature.com)
  • Mechanistic investigations demonstrated the key role of the identified genes in the balance between death and survival of tumor cells. (biomedcentral.com)
  • Interestingly, P-Tex cells expressed CDK4 genes as high as cancer cells, which could be simultaneously inhibited by CDK4 inhibitors and might be a potential reason for the ineffectiveness of CDK4 inhibitors in treating HPV-positive HNSCC. (elifesciences.org)
  • We employed TNF as being a proinflammatory cytokine to en hance TGFB induced EMT in our model system, and we discover that genes that propagate TNF signaling are upregulated and strongly enriched in GC16 and GC19. (pka-signal.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)
  • In the present study, our aim was to determine the time-dependent, ER-mediated apoptotic and autophagy induction of purvalanol in HCT 116 colon cancer cells. (spandidos-publications.com)
  • Moreover, we determined that during purvalanol-mediated ER stress, autophagic machinery was also activated prior to apoptotic cell death finalization. (spandidos-publications.com)
  • Olomoucine, roscovitine and purvalanol are examples of CDK inhibitors (CDKIs) designed and investigated for their apoptotic potential on cancer cells ( 3 ). (spandidos-publications.com)
  • Τheir impact on the apoptotic cell death mechanism requires further elucidation. (spandidos-publications.com)
  • Although purvalanol-induced cell cycle arrest and apoptotic cell death were demonstrated in prostate ( 5 ), breast ( 6 ) and colon cancer cells ( 7 ), the exact molecular mechanism of purvanol-induced apoptosis has not been elucidated yet. (spandidos-publications.com)
  • These results suggest prominent in vitro anti-proliferative and pro-apoptotic effects of ST in MDA-MB-231 cells. (biomedcentral.com)
  • 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)
  • 10 , 11 The major molecules responsible for G2/M transition are cyclin A /CDK1 and cyclin B/CDK1. (jcpjournal.org)
  • 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)
  • We demonstrate that miR-31 inhibits MCM2 expression via its 3'-untranslated region, that knockdown of MCM2 in DAOY cells leads to a degree of growth inhibition comparable to that by miR-31 restoration, and that overexpression of miR-31 reduces the chromatin loading of MCM2 at the point of G1/S transition. (oncotarget.com)
  • We had also found that ERK1c translocates to the Golgi at the G2 to M phase transition, but the molecular mechanism underlying this recruitment remains unknown. (biologists.com)
  • The degradation of cyclin F mediated by β-TrCP occurs at the G2/M transition. (ox.ac.uk)
  • Global gene expression profiling of mouse medulloblastomas and bioinformatics analyses of microRNA targets suggest that minichromosome maintenance complex component 2 (MCM2) is a likely target gene of miR-31 in suppressing cell growth. (oncotarget.com)
  • BRCA2 gene expression is tightly regulated during the cell cycle in human breast cells. (biomedcentral.com)
  • The expression of BRCA2 gene is silenced at the G0/G1 phase of cell growth and is de-silenced at the S/G2 phase. (biomedcentral.com)
  • Subcellular location of ZAR2 and its expression from the reverse promoter of the BRCA2 gene are stringently regulated in a cell cycle dependent manner. (biomedcentral.com)
  • ZAR2 binds to BRCA2/ZAR2 bi-directional promoter in vivo and is responsible, at least in part, for the silencing of BRCA2 gene expression in the G0/G1 phase in human breast cells. (biomedcentral.com)
  • The mutations of BRCA2 gene predispose the cells towards neoplastic development. (biomedcentral.com)
  • BRCA2 gene expression is stringently regulated during the cell cycle. (biomedcentral.com)
  • Bone marrow stem cells, including the pluripotent hematopoietic stem cells (HSCs) and bone mesenchymal stem cells (BMSCs), are being considered as potential targets for cell and gene therapy-based approaches against a variety of different diseases. (hindawi.com)
  • This gene may be involved in several cellular functions including growth, migration, aggregation and anti-inflammation in multiple cell types. (cancerindex.org)
  • HCT 116 colon cancer cells were exposed to purvalanol, which activated ER stress via upregulation of PERK, IRE1α gene expression, eIF-2α phosphorylation and ATF-6 cleavage at early time-points in the HCT 116 colon cancer cells. (spandidos-publications.com)
  • The most frequent rearrangement of the human MLL gene fuses MLL to AF4 resulting in high-risk infant B-cell acute lymphoblastic leukemia (B-ALL). (ibecbarcelona.eu)
  • These functional Golgi ministacks remain distributed about the cell, unable to track forward to form a perinuclear Golgi since nocodazole has depolymerized the microtubules. (wikipedia.org)
  • Golgi fragmentation is a highly regulated process that allows division of the Golgi complex between the two daughter cells. (biologists.com)
  • Animal study confirmed that β-peltatin significantly suppressed the growth of subcutaneously-implanted BxPC-3 cell xenografts. (biomedcentral.com)
  • 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)
  • A significantly increasing pattern of hypodiploid phases of cells also been observed, which confirm the apoptosis induction again. (phcogj.com)
  • In particular, the loss of ALKBH6 in human pancreatic cancer cells increases alkylating agent-induced DNA damage and significantly decreases cell survival. (frontiersin.org)
  • AXL significantly promotes tumour cell migration, invasion and metastasis, as well as angiogenesis. (cancerindex.org)
  • 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 survival prognosis of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) is largely different, and little is known about the anti-tumor mechanism of tumor-infiltrated exhausted CD8 + T cells (Tex) in HNSCC. (elifesciences.org)
  • The risk is increased 1000-fold for squamous cell carcinoma, basal cell carcinoma, malignant melanoma, and fibrosarcoma and is increased 10-fold to 20-fold for other tumors. (medscape.com)
  • In addition, proteome analysis of NBPF1-overexpressing DLD1 cells identified 32 differentially expressed proteins, of which several are implicated in carcinogenesis. (biomedcentral.com)
  • We demonstrated that NBPF1 exerts different tumor suppressive effects, depending on the cell line analyzed, and provide new clues into the molecular mechanism of the enigmatic NBPF proteins. (biomedcentral.com)
  • This phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. (docksci.com)
  • Here, the fusion proteins MLL-AF4 (MA4) and AF4-MLL (A4M) were CRISPR/Cas9-genome edited in the AAVS1 locus of HEK293 cells as a model to study MLL fusion-mediated DNA-DSB formation/repair. (ibecbarcelona.eu)
  • 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)
  • Overall, our data suggest that ALKBH6 is required to maintain the integrity of the genome and promote cell survival of pancreatic cancer cells. (frontiersin.org)
  • Rather, someimpactjournals.com/oncotargetfunction of BRCA1 - besides its intra-S and/or G2/M checkpoint activity - affects cell survival immediately after IR. (calcium-channel.com)
  • A proliferative exhausted CD8 + T cell cluster (P-Tex) which was beneficial to survival outcomes of patients with HPV-positive HNSCC was identified. (elifesciences.org)
  • however, purvalanol triggered autophagy, which functions as a cell survival mechanism at early time-points. (spandidos-publications.com)
  • The associations among CDK7, p38α, MYC, PD-L1, infiltrating T cells, and survival outcomes were validated in two tissue microarrays and public transcriptomic data of NSCLC. (biomedcentral.com)
  • Live-cell fluorescence microscopy (LCFM) is a powerful tool used to investigate cellular dynamics in real time. (biomedcentral.com)
  • Here we describe a widely applicable nontoxic approach for measuring DNA content in live cells by fluorescence microscopy. (biomedcentral.com)
  • To overcome this limitation, approaches incorporating laser scanning cytometry and fluorescence microscopy have been successful in quantifying DNA content in single cells [ 2 , 3 ], providing the capacity to combine this information with additional cellular parameters that can be elucidated by imaging. (biomedcentral.com)
  • Therefore, traditional methods for examining DNA content by microscopy have relied on cellular fixation, which is incompatible with tracking cells over time. (biomedcentral.com)
  • In budding yeast, individual chromosomes from vegetative cells cannot be visualized by microscopy. (silverchair.com)
  • Pds5p and the cohesin complex are required for sister chromatid cohesion and localize to the same chromosomal loci over the same cell cycle window. (silverchair.com)
  • It has been suggested that MLL fusions render cells susceptible to additional chromosomal damage upon exposure to etoposide. (ibecbarcelona.eu)
  • Although ATR inhibition was recently confirmed to show a synergistic inhibitory effect in PTEN-deficient triple-negative breast cancer cells, the molecular mechanism needs to be further elucidated. (bvsalud.org)
  • This study provides fundamental insight into the functional impact of CDK4 inhibition on cells in the tumor microenvironment, which is of high importance and interest to the field. (elifesciences.org)
  • In MDA-MB-231 cells, ST caused a significant dose-dependent cell growth inhibition by 31- 63% (p ≤ 0.0001) in 48 h and 40-50% (p ≤ 0.0001) in 72 h. (biomedcentral.com)
  • Flow cytometry was performed to detect the status of the immune microenvironment after CDK7 inhibition and antiPD-1 therapy in vivo. (biomedcentral.com)
  • Inhibition of miR-22-3p or ectopic MDC1 expression reversed the increased senescence, DNA damage, CIN and defective HR observed in AP4 -deficient CRC cells. (biomedcentral.com)
  • The increased cytotoxic activity is tied to the enhanced poly (ADP-ribose) polymerase (PARP) cleavage and consequently cell death due to the decrease in phosphorylation levels of checkpoint kinases 1 and 2 (CHK1/2), the reduction of radiation sensitive 51 (RAD51) foci and the increase in phosphorylation of the histone variant H2AX (γ-H2AX) foci (P (bvsalud.org)
  • We find that together with loss-of-function mutations in p53 and, to some degree, potentiated by cMyc overexpression, Dusp4 deletion aids in cell cycle checkpoint escape while simultaneously potentiating hallmarks of replicative stress, including multinucleation and Chk1 phosphorylation. (biomedcentral.com)
  • MAIN METHODS: Cytotoxicity was evaluated by cell viability assays. (bvsalud.org)
  • We demonstrate PTEN dysfunction promotes the killing effect of ATR blockade through the use of RNA interference for PTEN and a highly selective ATR inhibitor VE-821, and certify that VE-821 (1.0 µmol/L) aggravates cytotoxicity of cisplatin on breast cancer cells, especially PTEN-null MDA-MB-468 cells which show more chemoresistance than PTEN-expressing MDA-MB-231 cells. (bvsalud.org)
  • NK1.1 (Killer cell lectin-like receptor subfamily B, member 1, KLRB1, NKR-P1A, CD161, cluster of differentiation 161), refers to Natural Killer (NK) cells, lymphocytes that mediate cytotoxicity and secrete cytokines after immune stimulation. (thermofisher.com)
  • Collectively, results presented in this study demonstrated that the ST, which is used as a euphoritic substance of abuse also, has significant level of toxicity in human cells. (phcogj.com)
  • The CDK7/MYC/PD-L1 signature and infiltrating T cell status collectively stratified NSCLC patients into different risk groups. (biomedcentral.com)
  • PIG3 knockdown can suppress intra-S phase and G2/M checkpoints ( 8 ). (ijbs.com)
  • of c Abl signaling to MST kinases more builds the situation that c Abl can be a crucial regulator in neuronal cell death. (aktinhibitor.com)
  • Cancer cells that are defective in p53 function are deficient in their ability to transcriptionally upregulate the CDK inhibitor p21 after genotoxic stress. (nature.com)
  • This program makes it possible for us to simultaneously figure out each HRR (GFP) and NHEJ (DsRed) events across exactly the same cell population, delivering a method to figure out if NHEJ might compensate for the defective HRR observed with BRCA14P. (calcium-channel.com)
  • Cells had been released by mechanised disruption by moving the cells 15C20 moments through a cup pipette. (bms-911543.com)
  • This method relies on introducing a live-cell membrane-permeant DNA fluorophore, such as Hoechst 33342, into the culture medium of cells at the end of any live-cell imaging experiment and measuring each cell's integrated nuclear fluorescence to quantify DNA content. (biomedcentral.com)
  • We also describe and provide an automated Matlab-derived algorithm that measures the integrated nuclear fluorescence in each cell and subsequently plots these measurements into a cell cycle histogram for each frame imaged. (biomedcentral.com)
  • DNA content is accurately assessed on a single cell basis by measuring the integrated nuclear fluorescence of a fluorophore that binds to DNA stoichiometrically. (biomedcentral.com)
  • Cells were exposed to an incremental dose escalation of paclitaxel (2 nM) for approximately 2 passages, up to a final concentration of 25 nM, once paclitaxel resistance was achieved. (biomedcentral.com)
  • AP4 -deficiency also sensitized CRC cells to 5-FU treatment, whereas ectopic AP4 conferred resistance to 5-FU in a miR-22-3p and MDC1-dependent manner. (biomedcentral.com)
  • Here, we show that the genomic region surrounding human miR-31 at 9p21.3 is frequently deleted in many solid tumor cell lines, and reintroducing miR-31 into DAOY cells, a line of human medulloblastoma cells devoid of miR-31, strongly suppresses cell growth, causes cell cycle arrest at the G1/S boundary, and inhibits colony formation in vitro and xenograft tumorigenesis in nude mice. (oncotarget.com)
  • In the G0/G1 growth phase ZAR2 is predominantly located inside the nucleus of the breast cells, binds to the BRCA2 promoter and inhibits the expression of BRCA2. (biomedcentral.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)
  • Decreased expression of NBPF1 in neuroblastoma cell lines with loss of 1p36 heterozygosity and the marked decrease of anchorage-independent clonal growth of DLD1 colorectal carcinoma cells with induced NBPF1 expression further suggest that NBPF1 functions as tumor suppressor. (biomedcentral.com)
  • Here, we set out to determine the relevance of AP4 in human colorectal cancer (CRC) cells. (biomedcentral.com)
  • Autotransplanted mouse model of endometriosis showed lenvatinib treatment abrogated the increased lymphatic vessels development in the endometriotic lesion, enlarged retroperitoneal lymph nodes, and immune cells infiltration, indicating that blocking VEGF-C signaling can reduce local chronic inflammation and concomitantly endometriosis development. (endometriosistreatmentreport.com)
  • Indeed, the potent pathotropic migratory properties of BMSCs and ability to circumvent both the complications associated with immune rejection of allogenic cells and many of the moral reasons associated with embryonic stem cell use suggest that BMSCs are most promising stem cells as a potential target for the clinical use of genetically engineered stem cells [ 14 , 15 ]. (hindawi.com)
  • Recently, immune checkpoint blockade therapies (ICBs) targeting PD-1/PD-L1 axis have exhibited significant clinical benefits. (biomedcentral.com)
  • Notably, we found that the expression of the CHK1 phosphatase PP1α is increased in Spi1/PU.1-overexpressing cells. (oncotarget.com)
  • We investigated its cellular localization and found it in both cytosolic and nuclear extracts derived from HeLa cells (Fig. 1 a). (biomedcentral.com)
  • 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)
  • Recent mouse model studies have identified two populations of cells, namely the granule neuron progenitors in the external germinal layer and the multipluripotent neural stem cells likely from the dorsal brain stem [ 4 ], as the cellular origin of medulloblastoma. (oncotarget.com)
  • The ability to measure DNA content in single cells by means of LCFM would allow cellular stage and ploidy to be coupled with a variety of imaging directed analyses. (biomedcentral.com)
  • This method allows the examination of single-cell dynamics to be correlated with cellular stage and ploidy in a high-throughput fashion. (biomedcentral.com)
  • Its quantification serves to assess several cellular parameters including DNA ploidy and a cell's temporal location within the cell cycle [ 1 ]. (biomedcentral.com)
  • To overcome the limitations brought upon by cellular fixation, membrane-permeant DNA fluorophores were designed to stain DNA stoichiometrically in live-cells (supravital staining), enabling both the quantification of DNA content and the ability to track the movement of chromosomes over time. (biomedcentral.com)
  • this limitation has been overcome via ectopic expression of human telomerase reverse transcriptase (hTERT), the catalytic component of telomerase, to produce large quantities of these cells as an attractive source for cellular transplantation [ 16 - 18 ]. (hindawi.com)
  • Arrestins present elevated expression in differentiated cells and inhibit cellular responses to growth stimuli. (pka-signal.com)
  • The in vitro cellular uptake profile confirmed the absorption of VD3 in the breast cancer cell line MCF-7 with apparent apoptosis. (referencecitationanalysis.com)
  • Introduction/Background We aimed to compare gemcitabine vs. cisplatin in terms of DNA damage response, viability/apoptosis of malignant granulosa cells. (bmj.com)
  • Fifteen micromoles of purvalanol induced a reduction in cell viability by 20 and 35% within 24 and 48 h, respectively. (spandidos-publications.com)
  • Traditionally, reporting DNA content has been accomplished with a high degree of accuracy in large cell populations using flow cytometry, a technique that allows the proportion of cells in each phase of the cell cycle to be calculated in a high-throughput fashion. (biomedcentral.com)
  • Simultaneous staining of C57BL/6 spleen cells with PK136 and DX5 reveals coexpression of both markers by a majority of cells as well as presence of small populations of DX5+PK136- and DX5-PK136+ cells. (thermofisher.com)
  • These findings establish a mechanism for co-targeting DNA damage-induced cell cycle checkpoints in combination with repair of cisplatin-DNA lesions in vivo using RNAi nanocarriers, and motivate further exploration of ASL as a generalized strategy to improve cancer treatment. (nature.com)
  • 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)
  • Methodology Malignant granulosa tumour cell lines (COV434 and KGN) were used for the experiments. (bmj.com)
  • Calebin-A induced death of malignant peripheral nerve sheath tumor cells by activation of histone acetyltransferase. (cancerindex.org)
  • Because most tumors are deficient in one or more aspects of the function of the p53 tumor suppressor, either as a consequence of mutations within p53, or impairment of upstream and downstream modulators of p53 activity 19 , targeting MK2 has the potential to selectively enhance tumor cell killing without increasing the genotoxic effects of chemotherapy on normal p53-wild type tissues. (nature.com)
  • The use of human telomerase reverse transcriptase-immortalized bone marrow mesenchymal stromal cells (hTERT-BMSCs) as vehicles to deliver antinociceptive galanin (GAL) molecules into pain-processing centers represents a novel cell therapy strategy for pain management. (hindawi.com)
  • The use of cell lines as "biological minipumps" to chronically deliver antinociceptive molecules into the pain-processing centers of the spinal cord represents a newly developed technique for the treatment of pain [ 3 ]. (hindawi.com)
  • 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)
  • Additionally, whether the PTEN-deficient breast cancer cells are more preferentially sensitized than PTEN-wild type breast cancer cells to cisplatin plus ATR inhibitor remains unanswered. (bvsalud.org)
  • Two telomerase holoenzyme components, Est1p and Est2p, were preferentially enriched at short telomeres in late S/G2 phase, the time of telomerase action. (princeton.edu)
  • Injected lentiviral vector preferentially transduced splenic dendritic cells and resulted in long-term expression. (jci.org)
  • Cancer cells can grow unusually via limitless number of cell division and can avoid apoptosis. (jcpjournal.org)
  • LC-MS/MS analysis was used to investigate the proteome of DLD1 colon cancer cells with induced NBPF1 expression. (biomedcentral.com)
  • While exploring the molecular changes associated with strong ST efficacy in breast cancer cells, we observed that ST induced cell cycle arrest as well as cell death. (biomedcentral.com)
  • This study provides valuable insight into the chemopreventive efficacy and associated molecular alterations of ST in breast cancer cells whereas it had only moderate efficacy on lung cancer cells and did not show any considerable effect on skin cancer cells. (biomedcentral.com)
  • Flow cytometry analysis showed that VALD-3 triggered cell cycle arrest and induced apoptosis of breast cancer cells. (researchsquare.com)
  • 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)
  • Cell cycle analysis was carried out using flow cytometry. (bmj.com)
  • Analysis of the changes of migration and invasion, showed significant reduced LAPTM5 suppressed cell metastasis. (spandidos-publications.com)
  • The involvement of cell cycle check point arrest has been performed using flow cytometry analysis. (phcogj.com)
  • The compelling conclusion that proliferative exhausted T cells are associated with response in HPV+ head and neck cancer is supported by the cohort of 14 patients with paired tumor and adjacent normal tissue and rigorous bioinformatic analysis of nearly 50,000 single CD3+ T cell transcriptomes. (elifesciences.org)
  • Applications Reported: PK136 has been reported for use in flow cytometric analysis, depletion of NK cells, and in vitro functional studies. (thermofisher.com)
  • Applications Tested: The PK136 antibody has been tested by flow cytometric analysis of C57Bl/6 mouse splenocytes and can be used at less than or equal to 0.5 µg per test. (thermofisher.com)
  • For cell synchronization experiments, nocodazole is usually used at a concentration of 40-100 ng/mL of culture medium for a duration of 12-18 hours. (wikipedia.org)
  • As nocodazole affects the cytoskeleton, it is often used in cell biology experiments as a control: for example, some dominant negative Rho small GTPases cause a similar effect as nocodazole, and constitutively activated mutants often reverse or negate the effect. (wikipedia.org)
  • Nocodazole is frequently used in cell biology laboratories to synchronize the cell division cycle. (wikipedia.org)
  • However, the measurement of DNA content by flow cytometry provides little resolution to the biology of individual cells. (biomedcentral.com)
  • All cell lines were cultured in Dulbecco's modified eagles' medium (DMEM) supplemented with 2 mM glutamine and 10% heat inactivated fetal bovine serum (FBS) from Life Technologies (Carlsbad, CA) and maintained at 37°C in a 5% CO 2 atmosphere. (biomedcentral.com)
  • siRNA transfected cells had been serum starved for 24 48h, three days soon after transfection. (aktinhibitor.com)
  • Thus, determining how cells cope with replicative stress can help our understanding of oncogenesis and lead to the identification of new antitumor treatment targets. (oncotarget.com)