scholarly journals Inhibition by derivatives of diguanidines of cell proliferation in Ehrlich ascites cells grown in cultures

1980 ◽  
Vol 188 (2) ◽  
pp. 491-501 ◽  
Author(s):  
L Alhonen-Hongisto ◽  
H Pösö ◽  
J Jänne
Keyword(s):  
Growth Inhibition ◽  
Ehrlich Ascites Carcinoma ◽  
Tumour Cells ◽  
Polyamine Metabolism ◽  
Decarboxylase Activity ◽  
Subsequent Formation ◽  
Adenosylmethionine Decarboxylase ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Cells ◽  
In Cells

The anti-proliferative effects of 1,1′-[(methylethanediylidene)dinitrilo]diguanidine [methylglyoxal bis(guanylhydrazone)] and 1,1′-[(metHYLETHANEDIYLIDENE)dinitrilo]bis-(3-aminoguaNIDINE) HAVE BEEN STUDIED IN Ehrlich ascites carcinoma cells grown in suspension cultures. Both compounds are potent inhibitors of S-adenosyl-L-methionine decarboxylase from the tumour cells. In the presence of putrescine (but not in its absence), the inhibition produced by 1,1′-[methylethanediylidene)dinitrilo]bis-(3-aminoguanadine) was apparently irreversible, as judged by persistent depression of the enzyme activity even after extensive dialysis. The two compounds produced similar increases in adenosylmethionine decarboxylase activity, which resulted from a striking stabilization of the enzyme in cells grown in the presence of the drugs. The inhibitory effect of the two diguanidine derivatives on the synthesis of DNA and protein became evident after an exposure of 4–8 h. At that time, the only change seen in tumour polyamines in cells grown in the presence of the inhibitors was an increase in cellular putrescine. To find out whether the compounds initially interfered with the energy production of the tumour cells, the cultures were grown in the presence of uniformly labelled glucose, and the formation of lactate, as well as the oxidation of the sugar into CO2, were measured. The activation of glycolysis upon dilution of the tumour cells with fresh medium and the subsequent formation of labelled CO2 were siliar in control cells and in cells exposed to methylglyoxal bis(buanylhydrazone), 1,1′-[(methylethanediylidene)dinitrilo]bis-(3-aminoguanidine) or diaminopropanol. Only a marginal decrease in the cellular content of ATP was found in cells exposed to the inhibitors for 24 h. The diguanidine-induced growth inhibition was fully reversed by low concentrations of exogenous polyamines. However, the possibility remained that the reversal by polyamines was due to a decrease of intracellular diguanidine concentration. Our results indicate that the mode of action of 1,1′-[(methylethanediylidene)dinitrilo]bis-(3-aminoguanidine) is fully comparable to that of methylglyoxal bis(guanylhydrazone), as regards stabilization of adenosylmethionine decarboxylase and the appearance of growth inhibition in Ehrlich ascites cells. The data tend to support the view that both compounds apparently have an early anti-proliferative effect unrelated to polyamine metabolism.

scholarly journals Regulation of S-adenosylmethionine decarboxylase by polyamines in Ehrlich ascites-carcinoma cells grown in culture

1980 ◽  
Vol 190 (3) ◽  
pp. 747-754 ◽  
Author(s):  
Leena Alhonen-Hongisto
Keyword(s):  
Half Life ◽  
Ehrlich Ascites Carcinoma ◽  
Enzyme Synthesis ◽  
Tumour Cells ◽  
Transcriptional Level ◽  
Decarboxylase Activity ◽  
Adenosylmethionine Decarboxylase ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Tumour ◽  
Stimulation Of

1. The mechanism of stimulation of S-adenosylmethionine decarboxylase (EC 4.1.1.50) activity by inhibitors of ornithine decarboxylase (EC 4.1.1.17), namely dl-α-difluoromethylornithine, 1,3-diaminopropane and 1,3-diaminopropan-2-ol, was studied in Ehrlich ascites-tumour cells grown in suspension cultures. 2. Difluoromethylornithine and diaminopropane, although decreasing the content of putrescine and spermidine, markedly stimulated adenosylmethionine decarboxylase activity after exposure of the cells to the drugs for 8h, whereas the effect of diaminopropanol only became apparent many hours later. In tumour cells exposed to any of the inhibitors, a close negative correlation existed between the activity of adenosylmethionine decarboxylase and the intracellular concentration of spermidine and/or spermidine plus spermine, suggesting that a depletion of higher polyamines triggered enhancement of adenosylmethionine decarboxylase activity. 3. The mechanism of difluoromethylornithine- and diaminopropane-induced stimulation of adenosylmethionine decarboxylase involved (a) a marked increase in the apparent half-life of the enzyme and (b) an induction of enhanced enzyme synthesis. Diaminopropanol seemed to act solely via an induction mechanism. 4. The increased adenosylmethionine decarboxylase activity elicited by difluoromethylornithine could be restored to control values by micromolar concentrations of exogenous spermidine and spermine in 4h and by putrescine in 22h. In addition to the natural polyamines, elevated adenosylmethionine decarboxylase activity could be repressed by 3,3′-iminodipropylamine, a close analogue of spermidine, but not by non-physiological diamines. 5. Addition of spermidine and actinomycin D to cultures treated with difluoromethylornithine produced a comparable decay of enhanced adenosylmethionine decarboxylase activity (with an apparent half-life of about 2.5h), whereas the effect of cycloheximide was much more rapid. The present results suggest that polyamines may regulate adenosylmethionine decarboxylase at the transcriptional level of gene expression.

The effects of tumour cells on embryonic cell aggregation, adhesion and detachment

1978 ◽  
Vol 29 (1) ◽  
pp. 271-275
Author(s):  
D.E. Maslow ◽  
L. Weiss
Keyword(s):  
Aggregate Size ◽  
Cell Aggregation ◽  
Inhibitory Effect ◽  
Neural Retina ◽  
Embryonic Cell ◽  
Tumour Cells ◽  
Ehrlich Ascites ◽  
Initial Adhesion ◽  
Ehrlich Ascites Cells ◽  
Gyratory Shaker

The presence of small numbers of tumour cells inhibits the aggregation of embryonic chicken neural retina cells grown in gyratory shaker culture. The aggregation of neural retina cells was also inhibited by ascites cell medium. We investigated whether the inhibitory effect of the tumour cells on aggregate size is effected by inhibition of the initial adhesion or by enhancement of their separation. The number of neural retina cells adherent to microtest plate surfaces was significantly reduced after incubation with either Ehrlich ascites cells or cell-free, conditioned medium, while the percentage of cells removed from glass by shearing was unchanged under those conditions. These results suggest that the reduction in neural retina cell aggregate size produced by Ehrlich ascites cells and their products is due to partial inhibition of neural retina cell adhesion processes, as distinct from enhancement of separation.

scholarly journals Growth inhibition and apoptosis of Ehrlich ascites carcinoma cells by the methanol extract ofEucalyptus camaldulensis

2013 ◽  
Vol 52 (3) ◽  
pp. 281-290 ◽  
Author(s):  
Farhadul Islam ◽  
Hasina Khatun ◽  
Mahbuba Khatun ◽  
Shaikh Mohummad Mohsin Ali ◽  
Jahan Ara Khanam
Keyword(s):  
Growth Inhibition ◽  
Methanol Extract ◽  
Ehrlich Ascites Carcinoma ◽  
Carcinoma Cells ◽  
Ehrlich Ascites

scholarly journals The influence of nerve section on the metabolism of polyamines in rat diaphragm muscle

1981 ◽  
Vol 196 (2) ◽  
pp. 603-610 ◽  
Author(s):  
D Hopkins ◽  
K L Manchester
Keyword(s):  
Ornithine Decarboxylase ◽  
Normal Values ◽  
Methionine Adenosyltransferase ◽  
Diaphragm Muscle ◽  
Regulatory Mechanisms ◽  
Polyamine Metabolism ◽  
Decarboxylase Activity ◽  
Rat Diaphragm ◽  
Nerve Section ◽  
Adenosylmethionine Decarboxylase

Concentrations of spermidine, spermine and putrescine have been measured in rat diaphragm muscle after unilateral nerve section. The concentration of putrescine increased approx. 10-fold 2 days after nerve section, that of spermidine about 3-fold by day 3, whereas an increase in the concentration of spermine was only observed after 7-10 days. It was not possible to show enhanced uptake of either exogenous putrescine or spermidine by the isolated tissue during the hypertrophy. Consistent with the accumulation of putrescine, activity of ornithine decarboxylase increased within 1 day of nerve section, was maximally elevated by the second day and then declined. Synthesis of spermidine from [14C]putrescine and either methionine or S-adenosylmethionine bt diaphragm cytosol rose within 1 day of nerve section, but by day 3 had returned to normal or below normal values. Activity of adenosylmethionine decarboxylase similarly increased within 1 day of nerve section, but by day 3 had declined to below normal values. Activity of methionine adenosyltransferase was elevated throughout the period studied. The concentration of S-adenosylmethionine was likewise enhanced during hypertrophy. Administration of methylglyoxal bis(guanylhydrazone) produced a marked increase in adenosylmethionine decarboxylase activity and a large increase in putrescine concentration, but did not prevent the rise in spermidine concentration produced by denervation. Possible regulatory mechanisms of polyamine metabolism consistent with the observations are discussed.

scholarly journals Regulation of rRNA synthesis and processing in animal cells. Effect of nucleoside analogues

1982 ◽  
Vol 202 (2) ◽  
pp. 325-332 ◽  
Author(s):  
S Iapalucci-Espinoza ◽  
M T Franze-Fernandez
Keyword(s):  
Amino Acids ◽  
High Rate ◽  
Nucleoside Analogues ◽  
Rrna Synthesis ◽  
Complete Medium ◽  
Animal Cells ◽  
Rrna Transcription ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Cells ◽  
In Cells

The nucleoside analogues fluorouridine and fluorodeoxyuridine (both at 100 muM) and 8-azaguanine (at 500 muM) inhibit both rRNA transcription and processing in Ehrlich ascites cells. In BHK21 cells fluorodeoxyuridine has no effect on either rRNA maturation or transcription, whereas toyocamycin (at 2 microM) inhibits both processes in BHK21 cells and Ehrlich ascites cells. The drugs inhibit transcription in cells incubated in the complete medium, but have no effect on the decreased transcription in cells incubated in a medium without amino acids. This lack of effect cannot be explained by an altered uptake of the drugs in the amino acid-starved cells, since maturation of the rRNA precursor is affected in cells incubated in media with or without amino acids. The effect of the drugs on rRNA transcription is not the consequence of the inhibition of protein synthesis. The results lend support to the proposal that rRNA processing and transcription are co-ordinately controlled in cells with a high rate of rRNA synthesis.

scholarly journals Tumourigenicity, cell-surface glycoprotein changes and ornithine decarboxylase gene pattern in Ehrlich ascites-carcinoma cells

1985 ◽  
Vol 229 (3) ◽  
pp. 711-715 ◽  
Author(s):  
L Alhonen-Hongisto ◽  
A Kallio ◽  
R Sinervirta ◽  
O A Jänne ◽  
C G Gahmberg ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Line ◽  
Ornithine Decarboxylase ◽  
Ehrlich Ascites Carcinoma ◽  
Tumour Cells ◽  
Carcinoma Cells ◽  
Surface Glycoprotein ◽  
Cell Surface Glycoprotein ◽  
Phenotypic Changes ◽  
Ehrlich Ascites

We selected a 2-difluoromethylornithine-resistant Ehrlich ascites-carcinoma cell line that grows in the presence of 20 mM-difluoromethylornithine. These cells contain 10-20 times the normal amount of hybridizable sequences for ornithine decarboxylase (EC 4.1.1.17) in their genomic DNA. We used these gene-amplified cells, their revertant counterparts (grown in the absence of the drug after an established gene amplification) and tumour cells grown in the presence of putrescine to investigate the changes of ornithine decarboxylase gene pattern and simultaneously occurring phenotypic changes, such as tumourigenicity and the expression of cell-surface glycoproteins. In the tumour cells reverted back to the normal gene frequency, not only did the amplified sequences disappear, but there were also signs of gene re-arrangements seen as a ‘gene jump’, when a signal evidently moved to a heavier restriction fragment. Similar gene re-arrangement likewise occurred in cells exposed to putrescine. Although the wild-type tumour cells and the gene-amplified cells readily grew in the peritoneal cavity of mice, the revertant cells and the putrescine-treated cells had lost their tumourigenicity in mice. Gene-amplified tumour cells and the revertant cells showed distinct changes in their surface glycoprotein pattern in comparison with the parental cell line. These findings indicate that alterations of ornithine decarboxylase gene pattern/dosage may be associated with phenotypic changes possibly related to the tumourigenicity of these carcinoma cells.

scholarly journals Effect of Honey and Eugenol on Ehrlich Ascites and Solid Carcinoma

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Saravana Kumar Jaganathan ◽  
Dilip Mondhe ◽  
Z. A. Wani ◽  
Harish C. Pal ◽  
Mahitosh Mandal
Keyword(s):  
Tumor Growth ◽  
Growth Inhibition ◽  
Phenolic Content ◽  
Cancer Chemoprevention ◽  
Ehrlich Ascites Carcinoma ◽  
Mammary Adenocarcinoma ◽  
Tumor Growth Inhibition ◽  
Ehrlich Ascites ◽  
Phenolic Constituents ◽  
Solid Carcinoma

Ehrlich ascites carcinoma is a spontaneous murine mammary adenocarcinoma adapted to ascites form and carried in outbred mice by serial intraperitoneal (i/p) passages. The previous work from our laboratory showed that honey having higher phenolic content was potent in inhibiting colon cancer cell proliferation. In this work, we extended our research to screen the antitumor activity of two selected honey samples and eugenol (one of the phenolic constituents of honey) against murine Ehrlich ascites and solid carcinoma models. Honey containing higher phenolic content was found to significantly inhibit the growth of Ehrlich ascites carcinoma as compared to other samples. When honey containing higher phenolic content was given at 25% (volume/volume) intraperitoneally (i/p), the maximum tumor growth inhibition was found to be 39.98%. However, honey was found to be less potent in inhibiting the growth of Ehrlich solid carcinoma. On the other hand, eugenol at a dose of 100 mg/kg i/p was able to inhibit the growth of Ehrlich ascites by 28.88%. In case of solid carcinoma, eugenol (100 mg/kg; i/p) showed 24.35% tumor growth inhibition. This work will promote the development of honey and eugenol as promising candidates in cancer chemoprevention.

THE MECHANISM OF PYRIDINE NUCLEOTIDE SYNTHESIS IN EHRLICH ASCITES CARCINOMA AND HOST LIVER

1967 ◽  
Vol 45 (2) ◽  
pp. 179-190 ◽  
Author(s):  
J. Purko ◽  
H. B. Stewart
Keyword(s):  
Nicotinic Acid ◽  
Ehrlich Ascites Carcinoma ◽  
Pyridine Nucleotide ◽  
Host Liver ◽  
Nucleotide Synthesis ◽  
Tumor Bearing ◽  
Ehrlich Ascites ◽  
Metabolic Products ◽  
Ehrlich Ascites Cells ◽  
Specific Activities

Labeled nicotinamide–adenine dinucleotide (NAD) and nicotinic acid–adenine dinucleotide (NacAD) were identified following Dowex 2 (formate) chromatography of extracts of Ehrlich ascites cells and of livers of mice 3 and 6 h after injection of nicotinamide (Nam) (500 mg/kg) containing Nam-7-14C, and 3 h after injection of nicotinic acid (Nac) (50 mg/kg) containing Nac-7-14C into tumor-bearing animals. Labeled Nac mononucleotide (NacMN) was also identified in the liver extracts. The urinary metabolic products of the precursors were separated and partially characterized. Liver appeared to be somewhat more active in synthesis of NAD than tumor; the more efficient amidation of NacAD to NAD in liver probably contributes to this difference. The results are consistent with NacAD being an intermediate in NAD biosynthesis. Investigations of extracts of acetone powders of tumor provided evidence for two possible routes of synthesis (via NMN, and NacMN–NacAD): (1) Extracts incubated with Nam mononucleotide (NMN) and ATP formed NAD. (2) Extracts incubated with Nac-14C or Nam-14C with suitable supplementation gave rise to labeled NacMN, NacAD and NAD. These substances were isolated and their specific activities determined. Glutamine appeared to enhance NAD formation at the expense of NacAD. Although a net accumulation of NAD did not occur, the formation of Nam-14C from Nac-14C and the demonstration of NADase in the preparations suggested that NAD was formed but rapidly degraded.

THIOPURINE NUCLEOTIDE SYNTHESIS IN A 6-MP-RESISTANT SUBLINE OF THE EHRLICH ASCITES CARCINOMA AND GROWTH INHIBITION BY CERTAIN ANTIMETABOLITES

1960 ◽  
Vol 38 (10) ◽  
pp. 1129-1135 ◽  
Author(s):  
A. R. P. Paterson
Keyword(s):  
Growth Inhibition ◽  
Tumor Cells ◽  
Test Dose ◽  
Ehrlich Ascites Carcinoma ◽  
Tumor Line ◽  
Nucleotide Synthesis ◽  
Parent Line ◽  
Ehrlich Ascites ◽  
Ascites Tumors ◽  
Hydrolysis Of

A 6-MP-resistant subline of the Ehrlich ascites carcinoma has been characterized as cross-resistant to thioguanine and is more sensitive to azaserine than the parent tumor line. The resistant subline has retained the sensitivity to amethopterin shown by the parent tumor line. 6-MP riboside was no more effective than 6-MP in inhibiting the growth of the resistant cells.It was shown previously that cells of this resistant subline, in contrast to cells of the parent line, were unable to synthesize 6-MP nucleotide from a test dose of 6-MP injected into the ascitic fluid. In the present study it was shown that resistant cells were also unable to convert 6-MP riboside or thioguanine to their nucleotide derivatives, both of which were synthesized by the 6-MP-sensitive parent line of tumor cells. Similarities observed in the metabolism of 6-MP and 6-MP riboside and in their chemotherapeutic effects were probably due to the extensive hydrolysis of 6-MP riboside which took place in both ascites tumors.

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