Induction of Cyclin E and Inhibition of DNA Synthesis by the Novel Acronycine Derivative S23906-1 Precede the Irreversible Arrest of Tumor Cells in S Phase Leading to Apoptosis

2001 ◽  
Vol 60 (6) ◽  
pp. 1383-1391 ◽  
Author(s):  
Stéphane Léonce ◽  
Valérie Pérez ◽  
Stéphanie Lambel ◽  
Delphine Peyroulan ◽  
François Tillequin ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Tumor Cells ◽  
Cyclin E ◽  
S Phase ◽  
The Novel ◽  
Inhibition Of Dna Synthesis

Interferon inhibition of DNA synthesis and cell division

1972 ◽  
Vol 18 (2) ◽  
pp. 145-151 ◽  
Author(s):  
M. V. O'Shaughnessy ◽  
S. H. S. Lee ◽  
K. R. Rozee
Keyword(s):  
Cell Division ◽  
Antiviral Activity ◽  
Dna Synthesis ◽  
S Phase ◽  
Cell Suspensions ◽  
Depression Effect ◽  
Growth Depression ◽  
Synchronized Cells ◽  
Inhibition Of Dna Synthesis ◽  
New Protein

Using monodispersed cell suspensions, interferon preparations were shown to have both a lethal and a growth-depression effect in the same concentration range as that required for antiviral activity. In addition, synchronized cells treated with interferon respond by delaying their normal uptake of thymidine during S phase until after a period during which new protein is synthesized. Puromycin added during this period prevents both the synthesis of this protein and the subsequent synthesis of DNA.

Inhibition of DNA synthesis by a factor from ascites tumor cells

1977 ◽  
Vol 13 (10) ◽  
pp. 1195-1196 ◽  
Author(s):  
K. Rothbarth ◽  
G. Maier ◽  
E. Schöpf ◽  
D. Werner
Keyword(s):  
Dna Synthesis ◽  
Tumor Cells ◽  
Ascites Tumor ◽  
Inhibition Of Dna Synthesis

Hydroxyurea: Inhibition of DNA-Synthesis and Selective Susceptibility of S-Phase Cells In Vivo

1967 ◽  
Vol 17 (1) ◽  
pp. 5-8 ◽  
Author(s):  
F. S. Philips ◽  
H. S. Schwartz ◽  
S. S. Sternberg
Keyword(s):  
Dna Synthesis ◽  
Renal Excretion ◽  
Tissue Concentration ◽  
Tritiated Thymidine ◽  
S Phase ◽  
Cell Renewal ◽  
Cytotoxic Effects ◽  
Inhibition Of Dna Synthesis ◽  
Physiological Disposition

SummaryThe cytotoxic effects of hydroxyurea and of related hydroxamic acid derivatives in vivo are briefly described. They occur selectively in tissues with high rates of cell renewal and they are of brief duration. Tissue concentration of hydroxyurea diminish rapidly as the result of renal excretion and metabolism; there is a close temporal relation between the physiological disposition of the agents and the cytotoxic changes. Hydroxyurea induces an immediate inhibition of DNA synthesis in proliferating tisdsues such as thymus, small intestine, and regenerating liver. Autoradiographic studies of mouse duodenum using tritiated thymidine have shown that the lethal susceptibility to hydroxyurea is restricted to cells in the S-phase of the mitotic cycles. Cells in G1, G2, and M are not damaged by the agent.

scholarly journals Transient inhibition of DNA synthesis results in increased dihydrofolate reductase synthesis and subsequent increased DNA content per cell.

1986 ◽  
Vol 6 (10) ◽  
pp. 3373-3381 ◽  
Author(s):  
R N Johnston ◽  
J Feder ◽  
A B Hill ◽  
S W Sherwood ◽  
R T Schimke
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Gene Amplification ◽  
Dihydrofolate Reductase ◽  
Dna Content ◽  
S Phase ◽  
Phase Cell ◽  
Drug Inhibition ◽  
Specific Proteins ◽  
Inhibition Of Dna Synthesis

We examined the role that blockage of cells in the cell cycle may play in the stimulation of gene amplification and enhancement of drug resistance. We found that several different inhibitors of DNA synthesis, which were each able to block cells at the G1-S-phase boundary, induced an enhanced cycloheximide-sensitive synthesis of an early S-phase cell cycle-regulated enzyme, dihydrofolate reductase, and of other proteins as well. This response was specific, in that blockage at the G2 phase did not result in overproduction of the enzyme. When the cells were released from drug inhibition, DNA synthesis resumed, resulting in a cycloheximide-sensitive elevation in DNA content per cell. We speculate that the excess DNA synthesis (which could contribute to events detectable later as gene amplification) is a consequence of the accumulation of S-phase-specific proteins in the affected cells, which may then secondarily influence the pattern of DNA replication.

scholarly journals cAMP-mediated Inhibition of DNA Replication and S Phase Progression: Involvement of Rb, p21Cip1, and PCNA

2005 ◽  
Vol 16 (3) ◽  
pp. 1527-1542 ◽  
Author(s):  
Soheil Naderi ◽  
Jean Y.J. Wang ◽  
Tung-Ti Chen ◽  
Kristine B. Gutzkow ◽  
Heidi K. Blomhoff
Keyword(s):  
Dna Replication ◽  
Dna Synthesis ◽  
Cellular Proliferation ◽  
Kinase Activity ◽  
Antitumor Agents ◽  
Cell Types ◽  
S Phase ◽  
3T3 Fibroblasts ◽  
Phase Progression ◽  
Inhibition Of Dna Synthesis

cAMP exerts an antiproliferative effect on a number of cell types including lymphocytes. This effect of cAMP is proposed to be mediated by its ability to inhibit G1/S transition. In this report, we provide evidence for a new mechanism whereby cAMP might inhibit cellular proliferation. We show that elevation of intracellular levels of cAMP inhibits DNA replication and arrests the cells in S phase. The cAMP-induced inhibition of DNA synthesis was associated with the increased binding of p21Cip1to Cdk2-cyclin complexes, inhibition of Cdk2 kinase activity, dephosphorylation of Rb, and dissociation of PCNA from chromatin in S phase cells. The ability of cAMP to inhibit DNA replication and trigger release of PCNA from chromatin required Rb and p21Cip1proteins, since both processes were only marginally affected by increased levels of cAMP in Rb-/-and p21Cip1-/-3T3 fibroblasts. Importantly, the implications of cAMP-induced inhibition of DNA synthesis in cancer treatment was demonstrated by the ability of cAMP to reduce apoptosis induced by S phase–specific cytotoxic drugs. Taken together, these results demonstrate a novel role for cAMP in regulation of DNA synthesis and support a model in which activation of cAMP-dependent signaling protects cells from the effect of S phase–specific antitumor agents.

scholarly journals v-Jun Overrides the Mitogen Dependence of S-Phase Entry by Deregulating Retinoblastoma Protein Phosphorylation and E2F-Pocket Protein Interactions as a Consequence of Enhanced Cyclin E-cdk2 Catalytic Activity

2000 ◽  
Vol 20 (7) ◽  
pp. 2529-2542 ◽  
Author(s):  
W. Clark ◽  
E. J. Black ◽  
A. MacLaren ◽  
U. Kruse ◽  
N. LaThangue ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Protein Interactions ◽  
Cyclin E ◽  
Specific Inhibitor ◽  
Cyclin A ◽  
S Phase ◽  
Pocket Protein ◽  
Cdk2 Activity ◽  
Rb Phosphorylation ◽  
Phase Entry

ABSTRACT v-Jun accelerates G1 progression and shares the capacity of the Myc, E2F, and E1A oncoproteins to sustain S-phase entry in the absence of mitogens; however, how it does so is unknown. To gain insight into the mechanism, we investigated how v-Jun affects mitogen-dependent processes which control the G1/S transition. We show that v-Jun enables cells to express cyclin A and cyclin A-cdk2 kinase activity in the absence of growth factors and that deregulation of cdk2 is required for S-phase entry. Cyclin A expression is repressed in quiescent cells by E2F acting in conjunction with its pocket protein partners Rb, p107, and p130; however, v-Jun overrides this control, causing phosphorylated Rb and proliferation-specific E2F-p107 complexes to persist after mitogen withdrawal. Dephosphorylation of Rb and destruction of cyclin A nevertheless occur normally at mitosis, indicating that v-Jun enables cells to rephosphorylate Rb and reaccumulate cyclin A without exogenous mitogenic stimulation each time the mitotic “clock” is reset. D-cyclin–cdk activity is required for Rb phosphorylation in v-Jun-transformed cells, since ectopic expression of the cdk4- and cdk6-specific inhibitor p16 INK4A inhibits both DNA synthesis and cell proliferation. Despite this, v-Jun does not stimulate D-cyclin–cdk activity but does induce a marked deregulation of cyclin E-cdk2. In particular, hormonal activation of a conditional v-Jun–estrogen receptor fusion protein in quiescent, growth factor-deprived cells stimulates cyclin E-cdk2 activity and triggers Rb phosphorylation and DNA synthesis. Thus, v-Jun overrides the mitogen dependence of S-phase entry by deregulating Rb phosphorylation, E2F-pocket protein interactions, and ultimately cyclin A-cdk2 activity. This is the first report, however, that cyclin E-cdk2, rather than D-cyclin–cdk, is likely to be the critical Rb kinase target of v-Jun.

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