scholarly journals Growth control in cultured 3T3 fibroblasts. Assays of cell proliferation and demonstration of a growth inhibitory activity.

1979 ◽  
Vol 83 (3) ◽  
pp. 562-575 ◽  
Author(s):  
P A Steck ◽  
P G Voss ◽  
J L Wang
Keyword(s):  
Cell Proliferation ◽  
Inhibitory Activity ◽  
Gel Filtration ◽  
Growth Control ◽  
Inhibitory Effect ◽  
Cell Number ◽  
Target Cells ◽  
Similar Treatment ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

Treatment of sparse, proliferating cultures of 3T3 cells (target cells) with medium conditioned by exposure to density-inhibited 3T3 cultures resulted in an inhibition of growth and division in the target cells when compared to similar treatment with unconditioned medium (UCM). This differential effect of conditioned medium (CM) and UCM on target cells was demonstrated using three assay systems: (a) assessment of total cell number; (b) measurement of [3H]thymidine incorporated into acid-precipitable DNA; and (c) determination of the percentage of radioactively labeled nuclei in individual cells after incorporation of [3H]thymidine. The difference in the total incorporation of [3H]thymidine in CM-treated and UCM-treated cells was reflected by a difference in the percent of labeled cells. There was no differences in the average number of grains per labeled cell in the two cultures. Moreover, the inhibitory effect of the CM on target cell proliferation was reversible. Finally, this growth inhibitory activity can be collected in serum-free medium, precipitated by ammonium sulfate, and fractionated by gel filtration. In these purification procedures, the inhibitory activity was consistently found to be associated with the protein-containing fractions of the CM. No activity was found upon similar treatment with UCM. These results suggest that a system has been developed for the purification and molecular analysis of growth inhibitory factors that may mediate growth control in culture fibroblasts.

scholarly journals Growth control in cultured 3T3 fibroblasts II. Molecular properties of a fraction enriched in growth inhibitory activity.

1982 ◽  
Vol 92 (2) ◽  
pp. 523-530 ◽  
Author(s):  
P A Steck ◽  
J Blenis ◽  
P G Voss ◽  
J L Wang
Keyword(s):  
Inhibitory Activity ◽  
Specific Activity ◽  
Biological Properties ◽  
Target Cells ◽  
3T3 Cells ◽  
Cultured Fibroblasts ◽  
Similar Treatment ◽  
Inhibition Of Growth ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

Treatment of sparse, proliferating cultures of 3T3 cells with medium conditioned by exposure to density-inhibited 3T3 cultures resulted in an inhibition of growth and division in the target cells when compared to similar treatment with unconditioned medium. This growth inhibitory activity was fractionated by ammonium sulfate precipitation and gel filtration, yielding one fraction that was 35-fold enriched in specific activity. Analysis of the chemical and biological properties of this highly active fraction indicated that: (a) it is an endogenous cell product, synthesized by the 3T3 cells and shed into the medium; (b) it is a protein and its activity is sensitive to treatment with pronase; (c) the constituent polypeptide chains have molecular weights of 10,000 and 13,000; and (d) it is not cytotoxic and its effect on target cells are reversible. These results suggest that we have partially purified from conditioned medium an endogenous growth regulatory factor that may play a role in density-dependent inhibition of growth in cultured fibroblasts. We propose the term Fibroblast Growth Regulator to describe this class of molecules.

scholarly journals The inhibition of growth by chemical compounds

1942 ◽  
Vol 130 (860) ◽  
pp. 255-299 ◽  
Keyword(s):  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Biological Properties ◽  
Usual Sense ◽  
Carcinogenic Activity ◽  
Related Substances ◽  
Inhibition Of Growth ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Derivatives Of

In an extended investigation of the growth-inhibitory activity of carcinogenic compounds and related substances, over two hundred compounds were tested, including various 5-, 10- and 9 : 10-substituted benzanthracenes, dimethyl derivatives of anthracene, nitrogenous analogues of 1 : 2-benzanthracene, benzphenothiazines and dibenzphenothiazines, compounds related to 3 : 4-benzphenanthrene, dibenzfluorenes, dibenzcarbazoles, dibenzpyrenes, azonaphthalenes and related products, naphthylam ines and naphthaquinones, arsenonaphthalenes, derivatives of triphenylethylene, and diphenyl derivatives of indene, β -naphthindole and β -naphthofuran. A striking degree of correspondence was often shown by the inhibitory and carcinogenic activity of closely related com pounds (e. g. 5-alkyl benzanthracenes; dibenzfluorenes; dibenzphenanthrenes; 2 : 2'-azonaphthalene, 2 : 2'-diamino -1 : 1'-dinaphthyl and 3 : 4 : 5 : 6-dibenzcarbazole). However, no inhibitory activity was observed for certain carcinogenic 10- and 9 : 10- substituted benzanthracenes. On the other hand, inhibitory activity was noted in a few compounds (e. g. 1 : 2'-azonaphthalene) which have yielded few or no tum ours in exhaustive tests, and in some of a group of synthetic oestrogenic compounds which, although not carcinogenic in the usual sense, are nevertheless associated with the induction of individual types of tum our under special conditions. The relation between molecular structure and inhibitory activity depends in general upon an optimal degree of molecular complexity and upon certain more specific requirements. Nevertheless, the results obtained with derivatives of triphenylethylene suggest that inhibitory activity may still be shown by compounds diverging widely from the polycyclic structure and possessing only a skeletal resemblance. Diminution of inhibitory effect with increased substituent size was shown in the 5-alkyl benzanthracenes tested, although the same relation does not necessarily obtain for other positions. The influence of the nature of the substituent is seen (for example) in the contrast between 10-methyl-, 10-amino- and 10-cyano-l: 2-benzanthracene (inhibitory) and 10-isopropyl - 1:2-benzanthracene (inactive). Lastly, numerous experiments indicated that solubilization of an active compound usually entails decrease of activity, although certain apparent exceptions were encountered. In addition to the relationship between inhibitory activity and carcinogenicity, and that between both biological properties and chemical structure, consideration is also given to the mode of production of the inhibitory effect.

scholarly journals Kappacin, a Novel Antibacterial Peptide from Bovine Milk

2001 ◽  
Vol 45 (8) ◽  
pp. 2309-2315 ◽  
Author(s):  
Marina Malkoski ◽  
Stuart G. Dashper ◽  
Neil M. O'Brien-Simpson ◽  
Gert H. Talbo ◽  
Mary Macris ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
High Performance ◽  
Active Form ◽  
Bovine Milk ◽  
Gel Filtration ◽  
Reversed Phase ◽  
Inhibitory Peptide ◽  
Rp Hplc ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

ABSTRACT Caseinomacropeptide (CMP) is a heterogeneous C-terminal fragment (residues 106 to 169) of bovine milk κ-casein composed of glycosylated and phosphorylated forms of different genetic variants. We have demonstrated that CMP has growth-inhibitory activity against the oral opportunistic pathogens Streptococcus mutans andPorphyromonas gingivalis and against Escherichia coli. CMP was fractionated using reversed-phase high-performance liquid chromatography (RP-HPLC), and each fraction was tested for activity against S. mutans in a 96-well-plate broth assay. Fractions were characterized by N-terminal sequence analysis and mass spectrometry. The active form of CMP was shown to be the nonglycosylated, phosphorylated κ-casein (residues 106 to 169) [κ-casein(106–169)], which we have designated kappacin. Endoproteinase Glu-C was used to hydrolyze CMP, and the generated peptides were separated using RP-HPLC and gel filtration-HPLC and then tested for activity against S. mutans. The peptide Ser(P)149κ-casein-A(138–158) was the only peptide generated by endoproteinase Glu-C digestion that exhibited growth-inhibitory activity. Peptides corresponding to the sequences of the inhibitory peptide Ser(P)149κ-casein-A(138–158) and its nonphosphorylated counterpart κ-casein-A(138–158) were chemically synthesized and tested for antibacterial activity. The synthetic Ser(P)149 κ-casein-A(138–158) displayed growth-inhibitory activity against S. mutans(MIC, 59 μg/ml [26 μM]). The nonphosphorylated peptide, however, did not inhibit growth at the concentrations tested, indicating that phosphorylation is essential for activity.

scholarly journals Growth-inhibitory activity of lymphoid cell plasma membranes. II. Partial characterization of the inhibitor.

1984 ◽  
Vol 99 (4) ◽  
pp. 1227-1234 ◽  
Author(s):  
K C Stallcup ◽  
S J Burakoff ◽  
M F Mescher
Keyword(s):  
Tumor Cells ◽  
Inhibitory Activity ◽  
Lymphoid Cell ◽  
Plasma Membranes ◽  
Gel Filtration ◽  
Lymphoid Cells ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Membrane Components ◽  
A Minor

We have shown that plasma membranes from lymphoid cells have inhibitory activity for the growth of normal lymphocytes and lymphoid tumor cells (Stallcup, K. C., A. Dawson, and M. F. Mescher, J. Cell Biol. 99:1221-1226). This growth-inhibitory activity has been found to co-purify with major histocompatibility complex class I antigens (H-2K and D) when these cell surface glycoproteins are isolated from detergent lysates of cells by affinity chromatography on monoclonal antibody columns. When incorporated into liposomes, the affinity-purified H-2 antigens inhibited the growth of both normal lymphocytes and tumor cells at concentrations of 1-3 micrograms/ml. Inhibition was readily reversed upon removal of the liposomes from the cell cultures, even after several days of exposure of cells to the inhibitor. Inhibitory activity was insensitive to protease digestion or heat treatment, indicating that it was not due to the H-2 glycoproteins. This was confirmed by the demonstration that inhibitory activity could be separated from the H-2 protein by gel filtration in the presence of deoxycholate and could be extracted from membranes or H-2 antigen preparations with organic solvents. The results demonstrate that the growth-inhibitory component(s) of the plasma membrane is a minor lipid or lipid-like molecule which retains activity in the absence of other membrane components. The findings reported here and in the preceding article suggest that this novel membrane component may have a role in control of lymphoid cell growth, possibly mediated by cell contacts.

scholarly journals Effect of Zinc-Reversible Growth-Inhibitory Activity in Human Empyema Fluid on Antibiotic Microbicidal Activity

2000 ◽  
Vol 44 (1) ◽  
pp. 139-142 ◽  
Author(s):  
Peter G. Sohnle ◽  
Beth L. Hahn
Keyword(s):  
Inhibitory Activity ◽  
Microbial Growth ◽  
Inhibitory Effect ◽  
The Other ◽  
Microbicidal Activity ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Mueller Hinton ◽  
Staphyloccocus Aureus ◽  
Zinc Addition

ABSTRACT Abscess fluid supernatants have zinc-reversible microbial growth-inhibitory activity that is mediated by calprotectin, a zinc-binding protein. Because it inhibits microbial growth, this activity might interfere with killing by antibiotics that require their target organisms to be proliferating. In the present study, we cultured bacteria in human empyema fluid and used zinc to overcome the growth-inhibitory effect of calprotectin. We then compared the effect of zinc on killing by the beta-lactams ampicillin and cefazolin with that of the fluoroquinolone trovafloxacin, since the latter may be better able to kill nonproliferating organisms. In empyema fluid diluted 1:5 in normal saline, addition of zinc (30 μM) increased growth of two strains of Staphyloccocus aureus and two strains of Escherichia coli but did not affect the MICs or MBCs of the three antibiotics in Mueller-Hinton broth. For one strain of S. aureus, no effect of zinc was found on killing by either ampicillin or cefazolin. However, with the other strain ofS. aureus and both strains of E. coli, significant enhancement of killing by both drugs was observed with zinc addition. On the other hand, no effect on the killing of any of the organisms was observed for trovafloxacin when zinc was added. These results suggest that the zinc-reversible growth-inhibitory activity of abscess fluid may interfere with the microbicidal activity of antibiotics requiring proliferating target organisms, although antibiotics better able to kill nonproliferating organisms may be less affected by this phenomenon.

scholarly journals New Alkoxy Flavone Derivatives Targeting Caspases: Synthesis and Antitumor Activity Evaluation

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 129 ◽  
Author(s):  
Joana Moreira ◽  
Diana Ribeiro ◽  
Patrícia Silva ◽  
Nair Nazareth ◽  
Madalena Monteiro ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Inhibitory Activity ◽  
Alkyl Halide ◽  
Human Tumor ◽  
Inhibitory Effect ◽  
Synthetic Approach ◽  
Growth Inhibitory Effect ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Caspase 7

The antitumor activity of natural flavonoids has been exhaustively reported. Previously it has been demonstrated that prenylation of flavonoids allows the discovery of new compounds with improved antitumor activity through the activation of caspase-7 activity. The synthesis of twenty-five flavonoids (4–28) with one or more alkyl side chains was carried out. The synthetic approach was based on the reaction with alkyl halide in alkaline medium by microwave (MW) irradiation. The in vitro cell growth inhibitory activity of synthesized compounds was investigated in three human tumor cell lines. Among the tested compounds, derivatives 6, 7, 9, 11, 13, 15, 17, and 18 revealed potent growth inhibitory activity (GI50 < 10 μM), being the growth inhibitory effect of compound 13 related with a pronounced caspase-7 activation on MCF-7 breast cancer cells and yeasts expressing human caspase-7. A quantitative structure-activity relationship (QSAR) model predicted that hydrophilicity, pattern of ring substitution/shape, and presence of partial negative charged atoms were the descriptors implied in the growth inhibitory effect of synthesized compounds. Docking studies on procaspase-7 allowed predicting the binding of compound 13 to the allosteric site of procaspase-7.

scholarly journals Modifications on the Tetrahydroquinoline Scaffold Targeting a Phenylalanine Cluster on GPER as Antiproliferative Compounds against Renal, Liver and Pancreatic Cancer Cells

2021 ◽  
Vol 14 (1) ◽  
pp. 49
Author(s):  
David Méndez-Luna ◽  
Loreley Araceli Morelos-Garnica ◽  
Juan Benjamín García-Vázquez ◽  
Martiniano Bello ◽  
Itzia Irene Padilla-Martínez ◽  
...  
Keyword(s):  
Binding Site ◽  
Cell Lines ◽  
Cancer Cell ◽  
Inhibitory Activity ◽  
In Silico ◽  
Cancer Cell Lines ◽  
Pancreatic Cancer Cells ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
New Compounds

The implementation of chemo- and bioinformatics tools is a crucial step in the design of structure-based drugs, enabling the identification of more specific and effective molecules against cancer without side effects. In this study, three new compounds were designed and synthesized with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-tox) properties and high affinity for the G protein-coupled estrogen receptor (GPER) binding site by in silico methods, which correlated with the growth inhibitory activity tested in a cluster of cancer cell lines. Docking and molecular dynamics (MD) simulations accompanied by a molecular mechanics/generalized Born surface area (MMGBSA) approach yielded the binding modes and energetic features of the proposed compounds on GPER. These in silico studies showed that the compounds reached the GPER binding site, establishing interactions with a phenylalanine cluster (F206, F208 and F278) required for GPER molecular recognition of its agonist and antagonist ligands. Finally, a 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay showed growth inhibitory activity of compounds 4, 5 and 7 in three different cancer cell lines—MIA Paca-2, RCC4-VA and Hep G2—at micromolar concentrations. These new molecules with specific chemical modifications of the GPER pharmacophore open up the possibility of generating new compounds capable of reaching the GPER binding site with potential growth inhibitory activities against nonconventional GPER cell models.

Indole-3-carbinol inhibits the proliferation of colorectal carcinoma LoVo cells through activation of the apoptotic signaling pathway

2021 ◽  
pp. 096032712110214
Author(s):  
JY Lee ◽  
HM Lim ◽  
CM Lee ◽  
S-H Park ◽  
MJ Nam
Keyword(s):  
Colorectal Carcinoma ◽  
Cancer Cells ◽  
Inhibitory Activity ◽  
Annexin V ◽  
Fluorescein Isothiocyanate ◽  
Cell Counting ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Lovo Cells

Indole-3-carbinol (I3C) is a phytochemical that exhibits growth-inhibitory activity against various cancer cells. However, there are limited studies on the effects of I3C on colon cancer cells. In this study, the growth-inhibitory activity of I3C against the human colorectal carcinoma cell line (LoVo) was examined. The results of the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide, colony formation, and cell counting assays revealed that I3C suppressed the proliferation of LoVo cells. Microscopy and wound-healing analyses revealed that I3C affected the morphology and inhibited the migration of LoVo cells, respectively. I3C induced apoptosis and DNA fragmentation as evidenced by the results of fluorescein isothiocyanate-conjugated annexin V staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling assay, respectively. Additionally, I3C arrested the cell cycle at the G0/G1 phase and enhanced the reactive oxygen species levels. Western blotting analysis revealed that treatment with I3C resulted in the activation of apoptotic proteins, such as poly(ADP-ribose) polymerase, caspase-3, caspase-7, caspase-9, Bax, Bim, and p53 in LoVo cells. These results indicate that I3C induces apoptosis in LoVo cells by upregulating p53, leading to the activation of Bax and caspases. Taken together, I3C exerts cytotoxic effects on LoVo cells by activating apoptosis.

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