scholarly journals The Effect of Epigallocatechin Gallate (EGCG) and Metal Ions Corroded from Dental Casting Alloys on Cell Cycle Progression and Apoptosis in Cells from Oral Tissues

10.5772/38357 ◽  
2012 ◽  
Author(s):  
Jiansheng Su ◽  
Zhizen Quan ◽  
Wenfei Han ◽  
Lili Chen ◽  
Jiamei Gu
Keyword(s):  
Cell Cycle ◽  
Metal Ions ◽  
Cell Cycle Progression ◽  
Epigallocatechin Gallate ◽  
Cycle Progression ◽  
Dental Casting ◽  
Casting Alloys ◽  
Dental Casting Alloys ◽  
In Cells

Evaluation of GPER agonist G-1 combined with navitoclax in platinum-resistant and -sensitive ovarian cancer cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13563-e13563
Author(s):  
Dennis C. DeSimone ◽  
Trung T. Nguyen ◽  
Eugen Brailiou ◽  
John C. Taylor ◽  
Gabriela Cristina Brailoiu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Parp Cleavage ◽  
Ovarian Cancer Cells ◽  
Cycle Progression ◽  
Platinum Based Chemotherapy ◽  
Induced Apoptosis ◽  
In Cells

e13563 Background: Most ovarian cancer patients are treated with platinum-based chemotherapy but eventually relapse with incurable disease. The G protein-coupled estrogen receptor GPER (GPR30) mediates Ca2+ mobilization in response to estrogen and G-1, a synthetic agonist. Large and sustained Ca2+ responses can lead to mitochondrial Ca2+ overload and apoptosis. Hence, we evaluated whether G-1 could induce apoptosis in cisplatin-sensitive A2780 and isogenic cisplatin–resistant CP70 (14-fold resistant), C30 (70-fold resistant) and C200 (157-fold resistant) human ovarian cancer cells. Bcl-2 and Bcl-xL protect mitochondria from Ca2+overload, and were overexpressed in these cisplatin-resistant cells; thus we also examined combining the Bcl-2 family inhibitor navitoclax with G-1. Methods: Cytoplasmic [Ca2+]c and mitochondrial [Ca2+]m were monitored using microscopy and fluorescent Ca2+ probes. Cell cycle, apoptosis and mitochondrial membrane potential (MMP) were assessed by flow cytometry of propidium iodide, Annexin V and DiIC1(5) -stained cells. The intracellular Ca2+ chelator BAPTA was used to block Ca2+mobilization. Results: Expression of the 53kDa GPER but not the 38 kDa isoform progressively increased with increasing cisplatin resistance. G-1 elicited sustained [Ca2+]c rises that correlated with 53 kDa GPER expression, followed by rises in [Ca2+]m. In all cells, 2.5 μM G-1 blocked cell cycle progression at G2/M, inhibited proliferation, and induced apoptosis (A2780 > C30 > CP70 ≥ C200). G-1 induced p53, caspase-3 and PARP cleavage, and MMP loss. BAPTA prevented G-1’s cell cycle and apoptotic effects in cells showing large Ca2+ mobilization responses but did not in cells with small Ca2+responses. Combining navitoclax with G-1 superadditively decreased cell viability and increased apoptosis. Conclusions: G-1 blocked cell cycle progression and induced apoptosis via a Ca2+-dependent pathway in cells expressing high 53 kDa GPER levels, but via a Ca2+-independent pathway in cells with low 53 kDa GPER expression. G-1 also interacted cooperatively with naviticlax. Therefore, G-1 plus navitoclax shows potential for therapeutic use in platinum-sensitive and -resistant ovarian cancer.

Biocompatibility of Dental Casting Alloys

2002 ◽  
Vol 13 (1) ◽  
pp. 71-84 ◽  
Author(s):  
Werner Geurtsen
Keyword(s):  
Metal Ions ◽  
Pure Titanium ◽  
Orthodontic Appliances ◽  
Metallic Materials ◽  
Dental Casting ◽  
Periodontal Tissues ◽  
Casting Alloys ◽  
Dental Restorations ◽  
Dental Casting Alloys

Most cast dental restorations are made from alloys or commercially pure titanium (cpTi). Many orthodontic appliances are also fabricated from metallic materials. It has been documented in vitro and in vivo that metallic dental devices release metal ions, mainly due to corrosion. Those metallic components may be locally and systemically distributed and could play a role in the etiology of oral and systemic pathological conditions. The quality and quantity of the released cations depend upon the type of alloy and various corrosion parameters. No general correlation has been observed between alloy nobility and corrosion. However, it has been documented that some Ni-based alloys, such as beryllium-containing Ni alloys, exhibit increased corrosion, specifically at low pH. Further, microparticles are abraded from metallic restorations due to wear. In sufficient quantities, released metal ions—particularly Cu, Ni, Be, and abraded microparticles—can also induce inflammation of the adjacent periodontal tissues and the oral mucosa. While there is also some in vitro evidence that the immune response can be altered by various metal ions, the role of these ions in oral inflammatory diseases such as gingivitis and periodontitis is unknown. Allergic reactions due to metallic dental restorations have been documented. Ni has especially been identified as being highly allergenic. Interestingly, from 34% to 65.5% of the patients who are allergic to Ni are also allergic to Pd. Further, Pd allergy always occurrs with Ni sensitivity. In contrast, no study has been published which supports the hypothesis that dental metallic materials are mutagenic/genotoxic or might be a carcinogenic hazard to man. Taken together, very contradictory data have been documented regarding the local and systemic effects of dental casting alloys and metallic ions released from them. Therefore, it is of critical importance to elucidate the release of cations from metallic dental restorations in the oral environment and to determine the biological interactions of released metal components with oral and systemic tissues.

Functional and molecular identification of intermediate-conductance Ca2+-activated K+ channels in breast cancer cells: association with cell cycle progression

2004 ◽  
Vol 287 (1) ◽  
pp. C125-C134 ◽  
Author(s):  
Halima Ouadid-Ahidouch ◽  
Morad Roudbaraki ◽  
Philippe Delcourt ◽  
Ahmed Ahidouch ◽  
Nathalie Joury ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Membrane Potential ◽  
Current Density ◽  
Cell Cycle Progression ◽  
G1 Phase ◽  
Cycle Progression ◽  
Mcf 7 ◽  
In Cells

We have previously reported that the hEAG K+ channels are responsible for the potential membrane hyperpolarization that induces human breast cancer cell progression into the G1 phase of the cell cycle. In the present study, we evaluate the role and functional expression of the intermediate-conductance Ca2+-activated K+ channel, hIK1-like, in controlling cell cycle progression. Our results demonstrate that hIK1 current density increased in cells synchronized at the end of the G1 or S phase compared with those in the early G1 phase. This increased current density paralleled the enhancement in hIK1 mRNA levels and the highly negative membrane potential. Furthermore, in cells synchronized at the end of G1 or S phases, basal cytosolic Ca2+ concentration ([Ca2+]i) was also higher than in cells arrested in early G1. Blocking hIK1 channels with a specific blocker, clotrimazole, induced both membrane potential depolarization and a decrease in the [Ca2+]i in cells arrested at the end of G1 and S phases but not in cells arrested early in the G1 phase. Blocking hIK1 with clotrimazole also induced cell proliferation inhibition but to a lesser degree than blocking hEAG with astemizole. The two drugs were essentially additive, inhibiting MCF-7 cell proliferation by 82% and arresting >90% of cells in the G1 phase. Thus, although the progression of MCF-7 cells through the early G1 phase is dependent on the activation of hEAG K+ channels, when it comes to G1 and checkpoint G1/S transition, the membrane potential appears to be primarily dependent on the hIK1-activity level.

scholarly journals Mechanosensitive Expression of Lamellipodin Governs Cell Cycle Progression and Intracellular Stiffness

2020 ◽  
Author(s):  
Joseph A. Brazzo ◽  
Kwonmoo Lee ◽  
Yongho Bae
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Cycle Progression ◽  
Cellular Processes ◽  
M Phase ◽  
And Migration ◽  
In Cells

SUMMARYCells exhibit pathological behaviors in response to increased extracellular matrix (ECM) stiffness, including accelerated cell proliferation and migration [1–9], which are correlated with increased intracellular stiffness and tension [2, 3, 10–12]. The biomechanical signal transduction of ECM stiffness into relevant molecular signals and resultant cellular processes is mediated through multiple proteins associated with the actin cytoskeleton in lamellipodia [2, 3, 10, 11, 13]. However, the molecular mechanisms by which lamellipodial dynamics regulate cellular responses to ECM stiffening remain unclear. Previous work described that lamellipodin, a phosphoinositide- and actin filament-binding protein that is known mostly for controlling cell migration [14–21], promotes ECM stiffness-mediated early cell cycle progression [2], revealing a potential commonality between the mechanisms controlling stiffness-dependent cell migration and those controlling cell proliferation. However, i) whether and how ECM stiffness affects the levels of lamellipodin expression and ii) whether stiffness-mediated lamellipodin expression is required throughout cell cycle progression and for intracellular stiffness have not been explored. Here, we show that the levels of lamellipodin expression in cells are significantly increased by a stiff ECM and that this stiffness-mediated lamellipodin upregulation persistently stimulates cell cycle progression and intracellular stiffness throughout the cell cycle, from the early G1 phase to M phase. Finally, we show that both Rac activation and intracellular stiffening are required for the mechanosensitive induction of lamellipodin. More specifically, inhibiting Rac1 activation in cells on stiff ECM reduces the levels of lamellipodin expression, and this effect is reversed by the overexpression of activated Rac1 in cells on soft ECM. We thus propose that lamellipodin is a critical molecular lynchpin in the control of mechanosensitive cell cycle progression and intracellular stiffness.

scholarly journals Myxoma Virus M-T5 Protects Infected Cells from the Stress of Cell Cycle Arrest through Its Interaction with Host Cell Cullin-1

2005 ◽  
Vol 79 (16) ◽  
pp. 10750-10763 ◽  
Author(s):  
J. B. Johnston ◽  
G. Wang ◽  
J. W. Barrett ◽  
S. H. Nazarian ◽  
K. Colwill ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Regulatory Protein ◽  
Myxoma Virus ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Infected Cells ◽  
In Cells

ABSTRACT The myxoma virus (MV) M-T5 gene encodes an ankyrin repeat protein that is important for virus replication in cells from several species. Insight was gained into the molecular mechanisms underlying the role of M-T5 as a host range determinant when the cell cycle regulatory protein cullin-1 (cul-1) was identified as a cellular binding partner of M-T5 and found to colocalize with the protein in both nuclear and cytosolic compartments. Consistent with this interaction, infection with wild-type MV (vMyxlac) or a deletion mutant lacking M-T5 (vMyxT5KO) differentially altered cell cycle progression in a panel of permissive and nonpermissive cells. Cells infected with vMyxlac transitioned rapidly out of the G0/G1 phase and preferentially accumulated at the G2/M checkpoint, whereas infection with vMyxT5KO impeded progression through the cell cycle, resulting in a greater percentage of cells retained at G0/G1. Levels of the cul-1 substrate, p27/Kip-1, were selectively increased in cells infected with vMyxT5KO compared to vMyxlac, concurrent with decreased phosphorylation of p27/Kip-1 at Thr187 and decreased ubiquitination. Compared to cells infected with vMyxlac, cell death was increased in vMyxT5KO-infected cells following treatment with diverse stimuli known to induce cell cycle arrest, including infection itself, serum deprivation, and exposure to proteasome inhibitors or double-stranded RNA. Moreover, infection with vMyxlac, but not vMyxT5KO, was sufficient to overcome the G0/G1 arrest induced by these stimuli. These findings suggest that M-T5 regulates cell cycle progression at the G0/G1 checkpoint, thereby protecting infected cells from diverse innate host antiviral responses normally triggered by G0/G1 cell cycle arrest.

FGF-2 induces a failure of cell cycle progression in cells harboring amplified K-Ras, revealing new insights into oncogene-induced senescence

2021 ◽  
Author(s):  
Peder J. Lund ◽  
Mariana Lopes ◽  
Simone Sidoli ◽  
Mariel Coradin ◽  
Francisca Nathália de Luna Vitorino ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Cell Cycle Progression ◽  
Growth Factor Signaling ◽  
Cycle Progression ◽  
Oncogenic Ras ◽  
P Cells ◽  
In Cells

Cells harboring oncogenic Ras were profiled with multi-omics to understand why they senesce instead of proliferate in response to growth factor signaling.

scholarly journals Caffeine overcomes a restriction point associated with DNA replication, but does not accelerate mitosis.

1990 ◽  
Vol 110 (6) ◽  
pp. 1855-1859 ◽  
Author(s):  
C S Downes ◽  
S R Musk ◽  
J V Watson ◽  
R T Johnson
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Cycle Progression ◽  
Normal Cycle ◽  
Restriction Point ◽  
Nuclear Structures ◽  
Mitotic Chromosome Condensation ◽  
In Cells

Mitotic chromosome condensation is normally dependent on the previous completion of replication. Caffeine spectacularly deranges cell cycle controls after DNA polymerase inhibition or DNA damage; it induces the condensation, in cells that have not completed replication, of fragmented nuclear structures, analogous to the S-phase prematurely condensed chromosomes seen when replicating cells are fused with mitotic cells. Caffeine has been reported to induce S-phase condensation in cells where replication is arrested, by accelerating cell cycle progression as well as by uncoupling it from replication; for, in BHK or CHO hamster cells arrested in early S-phase and given caffeine, condensed chromosomes appear well before the normal time at which mitosis occurs in cells released from arrest. However, we have found that this apparent acceleration depends on the technique of synchrony and cell line employed. In other cells, and in synchronized hamster cells where the cycle has not been subjected to prolonged continual arrest, condensation in replication-arrested cells given caffeine occurs at the same time as normal mitosis in parallel populations where replication is allowed to proceed. This caffeine-induced condensation is therefore "premature" with respect to the chromatin structure of the S-phase nucleus, but not with respect to the timing of the normal cycle. Caffeine in replication-arrested cells thus overcomes the restriction on the formation of mitotic condensing factors that is normally imposed during DNA replication, but does not accelerate the timing of condensation unless cycle controls have previously been disturbed by synchronization procedures.

scholarly journals Cdc28 tyrosine phosphorylation and the morphogenesis checkpoint in budding yeast.

1996 ◽  
Vol 7 (11) ◽  
pp. 1657-1666 ◽  
Author(s):  
R A Sia ◽  
H A Herald ◽  
D J Lew
Keyword(s):  
Cell Cycle ◽  
Translational Regulation ◽  
Cell Cycle Progression ◽  
Nuclear Division ◽  
Budding Yeast ◽  
Mrna Levels ◽  
Gene Encoding ◽  
Cycle Progression ◽  
Morphogenesis Checkpoint ◽  
In Cells

A morphogenesis checkpoint in budding yeast delays nuclear division (and subsequent cell cycle progression) in cells that have failed to make a bud. We show that the ability of this checkpoint to delay nuclear division requires the SWE1 gene, encoding a protein kinase that inhibits the master cell cycle regulatory kinase Cdc28. The timing of nuclear division in cells that cannot make a bud is exquisitely sensitive to the dosage of SWE1 and MIH1 genes, which control phosphorylation of Cdc28 at tyrosine 19. In contrast, the timing of nuclear division in budded cells does not rely on Cdc28 phosphorylation, suggesting that the morphogenesis checkpoint somehow turns on this regulatory pathway. We show that SWE1 mRNA levels fluctuate during the cell cycle and are elevated in cells that cannot make a bud. However, regulation of SWE1 mRNA levels by the checkpoint is indirect, acting through a feedback loop requiring Swe1 activity. Further, the checkpoint is capable of delaying nuclear division even when SWE1 transcription is deregulated. We propose that the checkpoint delays nuclear division through post-translational regulation of Swe1 and that transcriptional feedback loops enhance the efficacy of the checkpoint.

scholarly journals A novel suppressor of ras1 in fission yeast, byr4, is a dosage-dependent inhibitor of cytokinesis.

1996 ◽  
Vol 133 (6) ◽  
pp. 1307-1319 ◽  
Author(s):  
K Song ◽  
K E Mach ◽  
C Y Chen ◽  
T Reynolds ◽  
C F Albright
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Mitotic Cell ◽  
Genetic Interactions ◽  
Null Alleles ◽  
Gene Products ◽  
Actin Ring ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
In Cells

A novel gene, designated byr4, was identified in Schizosaccharomyces pombe that affects the mitotic cell cycle and shows genetic interactions with the ras1 signaling pathways. Null alleles of byr4 cause cell cycle arrest in late mitosis and permit multiple rounds of septation. The multiple septa typically divide two nuclei, but the nuclei frequently do not stain equally with 4',6-diamidino-2-phenylindole (DAPI), suggesting that byr4 is required for proper karyokinesis. Overexpression of byr4 inhibits cytokinesis, but cell cycle progression continues leading to multinucleate cells. When byr4 is overexpressed, the early steps in the cytokinesis pathway, including formation of the medial F-actin ring, occur normally; however, the later steps in the pathway, including contraction of the F-actin ring, septation, and rearrangement of the medial F-actin following mitosis, rarely occur, byr4 shows two genetic interactions with ras1. The inhibition of cytokinesis by byr4 overexpression was exacerbated by null alleles of ras1 and scd1, suggesting a link between pathways needed for cell polarity and cytokinesis. Overexpression of byr4 also partially bypasses the need for ras1 for sporulation. The electrophoretic mobility of the byr4 protein varied in response to mutants that perturb cytokinesis and karyokinesis, suggesting interactions between byr4 and these gene products. A more rapidly migrating byr4 protein was found in cells with mutations in cdc16, which undergo repeated septation, and in cdc15, which fail to form a medial F-actin ring in mitosis. A slower migrating byr4 protein was found in cells with a mutation in the beta-tubulin gene, which arrests cells at the metaphase-anaphase transition.

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