Clonal variation of cadmium response in human tumor cell lines

1986 ◽  
Vol 250 (2) ◽  
pp. C256-C263 ◽  
Author(s):  
M. D. Enger ◽  
J. G. Tesmer ◽  
G. L. Travis ◽  
S. S. Barham
Keyword(s):  
Cell Lines ◽  
Human Fibroblasts ◽  
Human Tumor ◽  
Clonal Variation ◽  
Parental Line ◽  
Early Passage ◽  
Normal Human ◽  
Dna Histograms

Subpopulations of human tumor-derived cell lines A101D, A204, and A549 were screened for Cd2+ cytotoxic response. Three of six A549, two of seven A101D, and four of seven A204 subpopulations were found to differ significantly from the parental line. A variant subpopulation of A101D (T3) was shown by flow cytometry to be comprised of cells having two distinct DNA histograms. One histogram, type 1, resembles that of normal human fibroblasts. The other, type 2, represents cells with one-third more DNA. Early passage T3 clonal populations were comprised primarily of type 1 cells. With passage, type 1 cells decreased relative to type 2 so that by passage 47 the culture was predominantly type 2. Correspondingly, the A101D T3 subpopulation became more Cd2+ sensitive with time in culture. Subclones having only type 1 DNA histograms were found to be Cd2+ resistant relative to subclones with type 2 histograms, and treatment of A101D T3 cultures having approximately equal amounts of type 1 and 2 cells with 2 microM Cd2+ resulted in the selection of type 1 cells. The enhanced Cd2+ resistance phenotype shown by A101D T3 type 1 cells correlated with reduced Cd2+ uptake and is not attributable to enhanced metallothionein synthesis.

scholarly journals Design, Synthesis, and Structural Characterization of Novel Diazaphenothiazines with 1,2,3-Triazole Substituents as Promising Antiproliferative Agents

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4388 ◽  
Author(s):  
Morak-Młodawska ◽  
Pluta ◽  
Latocha ◽  
Jeleń ◽  
Kuśmierz
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Human Fibroblasts ◽  
Human Tumor ◽  
Design Synthesis ◽  
Human Tumor Cell Lines ◽  
Ic50 Values ◽  
Normal Human ◽  
Low Cytotoxicity

A series of novel 1,2,3-triazole-diazphenothiazine hybrids was designed, synthesized, and evaluated for anticancer activity against four selected human tumor cell lines (SNB-19, Caco-2, A549, and MDA-MB231). The majority of the synthesized compounds exhibited significant potent activity against the investigated cell lines. Among them, compounds 1d and 4c showed excellent broad spectrum anticancer activity, with IC50 values ranging from 0.25 to 4.66 μM and 0.25 to 6.25 μM, respectively. The most promising compound 1d, possessing low cytotoxicity against normal human fibroblasts NHFF, was used for gene expression analysis using reverse transcription–quantitative real-time PCR (RT–qPCR). The expression of H3, TP53, CDKN1A, BCL-2, and BAX genes revealed that these compounds inhibited the proliferation in all cells (H3) and activated mitochondrial events of apoptosis (BAX/BCL-2).

scholarly journals Synthesis and Evaluation of Anticancer Activities of Novel C-28 Guanidine-Functionalized Triterpene Acid Derivatives

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 3000 ◽  
Author(s):  
Anna Spivak ◽  
Rezeda Khalitova ◽  
Darya Nedopekina ◽  
Lilya Dzhemileva ◽  
Milyausha Yunusbaeva ◽  
...  
Keyword(s):  
Human Fibroblasts ◽  
Human Tumor ◽  
Jurkat Cells ◽  
Anticancer Activities ◽  
Triterpene Acid ◽  
Guanidine Group ◽  
Triterpene Acids ◽  
Cycle Arrest ◽  
Normal Human ◽  
Derivatives Of

Triterpene acids, namely, 20,29-dihydrobetulinic acid (BA), ursolic acid (UA) and oleanolic acid (OA) were converted into C-28-amino-functionalized triterpenoids 4–7, 8a, 15, 18 and 20. These compounds served as precursors for the synthesis of novel guanidine-functionalized triterpene acid derivatives 9b–12b, 15c, 18c and 20c. The influence of the guanidine group on the antitumor properties of triterpenoids was investigated. The cytotoxicity was tested on five human tumor cell lines (Jurkat, K562, U937, HEK, and Hela), and compared with the tests on normal human fibroblasts. The antitumor activities of the most tested guanidine derivatives was lower, than that of corresponding amines, but triterpenoids with the guanidine group were less toxic towards human fibroblasts. The introduction of the tris(hydroxymethyl)aminomethane moiety into the molecules of triterpene acids markedly enhanced the cytotoxic activity of the resulting conjugates 15, 15c, 18b,c and 20b,c irrespective of the triterpene skeleton type. The dihydrobetulinic acid amine 15, its guanidinium derivative 15c and guanidinium derivatives of ursolic and oleanolic acids 18c and 20c were selected for extended biological investigations in Jurkat cells, which demonstrated that the antitumor activity of these compounds is mediated by induction of cell cycle arrest at the S-phase and apoptosis.

Chromosome 7 suppresses indefinite division of nontumorigenic immortalized human fibroblast cell lines KMST-6 and SUSM-1

1993 ◽  
Vol 13 (10) ◽  
pp. 6036-6043
Author(s):  
T Ogata ◽  
D Ayusawa ◽  
M Namba ◽  
E Takahashi ◽  
M Oshimura ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cell ◽  
Human Fibroblasts ◽  
Fibroblast Cell ◽  
Chromosome 7 ◽  
In Vitro Mutagenesis ◽  
Human Cell Lines ◽  
First Case ◽  
Normal Human

Using nontumorigenic immortalized human cell lines KMST-6 (KMST) and SUSM-1 (SUSM), we attempted to identify the chromosome that carries a putative senescence-related gene(s). These cell lines are the only ones that have been established independently from normal human diploid fibroblasts following in vitro mutagenesis. We first examined restriction fragment length polymorphisms on each chromosome of these immortalized cell lines and their parental cell lines and found specific chromosomal alterations common to these cell lines (a loss of heterozygosity in KMST and a deletion in SUSM) on the long arm of chromosome 7. In addition to these, we also found that introduction of chromosome 7 into these cell lines by means of microcell fusion resulted in the cessation of cell division, giving rise to cells resembling cells in senescence. Introduction of other chromosomes, such as chromosomes 1 and 11, on which losses of heterozygosity were also detected in one of the cell lines (KMST), to either KMST or SUSM cells or of chromosome 7 to several tumor-derived cell lines had no effect on their division potential. These results strongly suggest that a gene(s) affecting limited-division potential or senescence of normal human fibroblasts is located on chromosome 7, probably at the long arm of the chromosome, representing the first case in which a specific chromosome reverses the immortal phenotype of otherwise normal human cell lines.

scholarly journals Differential expression and regulation of ryanodine receptor and myo-inositol 1,4,5-trisphosphate receptor Ca2+ release channels in mammalian tissues and cell lines

1997 ◽  
Vol 327 (1) ◽  
pp. 251-258 ◽  
Author(s):  
John J. MACKRILL ◽  
R. A. John CHALLISS ◽  
D. A. O'CONNELL ◽  
F. Anthony LAI ◽  
Stefan R. NAHORSKI
Keyword(s):  
Cell Lines ◽  
Mammalian Cell ◽  
Release Channel ◽  
Chronic Stimulation ◽  
Channel Proteins ◽  
Mammalian Cell Lines ◽  
Rabbit Tissues ◽  
Stimulation Of

Ryanodine receptors (RyRs) and Ins(1,4,5)P3 receptors (Ins(1,4,5)P3Rs) represent two multigene families of channel proteins that mediate the release of Ca2+ ions from intracellular stores. In the present study, the expression patterns of these channel proteins in mammalian cell lines and tissues were investigated by using isoform-specific antibodies. All cell lines examined expressed two or more Ins(1,4,5)P3R isoforms, with the type 1 Ins(1,4,5)P3R being ubiquitous. RyR isoforms were detected in only six out of eight cell lines studied. Similarly, of the nine rabbit tissues examined, RyR protein expression was detected only in brain, heart, skeletal muscle and uterus. Specific [3H]ryanodine binding was found in a number of rabbit tissues, although it was not detected in mammalian cell lines. Subcellular fractionation of SH-SY5Y human neuroblastomas revealed that the type 2 RyR and type 1 Ins(1,4,5)P3R co-localize among the fractions of a sucrose-cushion separation of crude microsomal membrane fractions. Manipulation of SH-SY5Y cells by chronic stimulation of muscarinic acetylcholine receptor (mAChR) results in a decrease in their type 1 Ins(1,4,5)P3R levels but not in the abundance of the type 2 RyR. Differentiation of these neuroblastomas by using retinoic acid did not detectably alter their expression of Ca2+-release channel proteins. Finally, differentiation of BC3H1 cells affects the expression of their Ca2+-release channel proteins in an isoform-specific manner. In summary, this study demonstrates that mammalian cell lines display distinct patterns of Ca2+-release channel protein expression. The abundance of these proteins is differentially regulated during phenotypic modifications of a cell, such as differentiation or chronic stimulation of mAChR.

scholarly journals Proliferative responses to altered 17β-hydroxysteroid dehydrogenase (17HSD) type 2 expression in human breast cancer cells are dependent on endogenous expression of 17HSD type 1 and the oestradiol receptors

2006 ◽  
Vol 13 (3) ◽  
pp. 875-884 ◽  
Author(s):  
A Jansson ◽  
C Gunnarsson ◽  
O Stål
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cell Lines ◽  
Hydroxysteroid Dehydrogenase ◽  
S Phase ◽  
Phase Fraction ◽  
Mcf7 Cells ◽  
Endogenous Expression

The primary source of oestrogen in premenopausal women is the ovary but, after menopause, oestrogen biosynthesis in peripheral tissue is the exclusive site of formation. An enzyme group that affects the availability of active oestrogens is the 17β-hydroxysteroid dehydrogenase (17HSD) family. In breast cancer, 17HSD type 1 and type 2 have been mostly investigated and seem to be the principal 17HSD enzymes involved thus far. The question whether 17HSD type 1 or type 2 is of greatest importance in breast tumour development is still not clear. The aim of this study was to investigate how the loss of 17HSD type 2 expression, using siRNA in the non-tumour breast epithelial cells HMEC (human mammal epithelial cells) and MCF10A, and gain of 17HSD type 2 expression, using transient transfection in the breast cancer derived cell lines MCF7 and T47D, affect oestradiol conversion and proliferation rate measured as S-phase fraction. We further investigated how this was related to the endogenous expression of 17HSD type 1 and oestradiol receptors in the examined cell lines. The oestradiol level in the medium changed significantly in the MCF7 transfected cells and the siRNA-treated HMEC cells, but not in T47D or MCF10A. The S-phase fraction decreased in the 17HSD type 2-transfected MCF7 cells and the siRNA-treated HMEC cells. The results seemed to be dependent on the endogenous expression of 17HSD type 1 and the oestradiol receptors. In conclusion, we found that high or low levels of 17HSD type 2 affected the oestradiol concentration significantly. However, the response was dependent on the endogenous expression of 17HSD type 1. Expression of 17HSD type 1 seems to be dominant to 17HSD type 2. Therefore, it may be important to investigate a ratio between 17HSD type 1 and 17HSD type 2.

scholarly journals Expression of colony-stimulating factor genes by normal human mesothelial cells and human malignant mesothelioma cells lines in vitro

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 940-946 ◽  
Author(s):  
GD Demetri ◽  
BW Zenzie ◽  
JG Rheinwald ◽  
JD Griffin
Keyword(s):  
Cell Lines ◽  
Malignant Mesothelioma ◽  
Interleukin 1 ◽  
Mesothelial Cells ◽  
Biologically Active ◽  
Northern Analysis ◽  
Early Passage ◽  
Gm Csf ◽  
Normal Human ◽  
Mesothelioma Cell

We investigated normal human mesothelial cells and human malignant mesothelioma cell lines for the ability to produce hematopoietic colony- stimulating factors (CSFs) in culture. Early passage cultures of normal diploid human mesothelial cells spontaneously expressed detectable levels of M-CSF mRNA transcripts, but lacked detectable transcripts for GM-CSF or G-CSF. Exposure of normal mesothelial cells to epidermal growth factor (EGF), lipopolysaccharide (LPS), or tumor necrosis factor (TNF) induced expression of G-CSF mRNA. The combination of EGF and TNF induced threefold more G-CSF transcripts than did either factor alone. GM-CSF transcripts were induced only by the combination of TNF and EGF. Interleukin-1 beta (IL-1 beta) transcripts were induced by EGF, TNF, or LPS and were inhibited by hydrocortisone (HC). All malignant mesothelioma cell lines tested also spontaneously expressed M-CSF transcripts. However, in contrast to normal mesothelial cells, two of four malignant mesothelioma cell lines also autonomously expressed G- CSF and GM-CSF transcripts without TNF, EGF, or LPS stimulation. Secretion of biologically active CSFs was confirmed by testing media conditioned by the various cell types examined. The detection of biologically active CSFs correlated well with the presence of detectable CSF transcripts by Northern analysis. These data indicate that (a) normal human mesothelial cells spontaneously express detectable levels of M-CSF mRNA in culture; (b) EGF is an essential cofactor for optimal induction of G-CSF and GM-CSF expression; (c) exposure of normal mesothelial cells to inflammatory mediators such as LPS and TNF increases the levels of transcripts for CSFs and IL-1 beta; and (d) as compared with normal human mesothelial cells, some cell lines of human malignant mesothelioma exhibit aberrant gene expression for multiple cytokines, including G-CSF, GM-CSF, IL-1 beta, and IL-6.

scholarly journals The selective toxic effect of dialdehyde derivatives of the pyrimidine nucleosides on human tumor cells

2015 ◽  
Vol 61 (4) ◽  
pp. 497-502 ◽  
Author(s):  
A.S. Efremova ◽  
S.I. Shram ◽  
M.S. Drenichev ◽  
G.A. Posypanova ◽  
N.F. Myasoedov ◽  
...  
Keyword(s):  
Toxic Effect ◽  
Tumor Cells ◽  
Human Fibroblasts ◽  
Human Tumor ◽  
Lung Fibroblasts ◽  
Growth And Survival ◽  
Cultured Human Fibroblasts ◽  
Normal Human ◽  
The Impact ◽  
Derivatives Of

The impact of a number of synthetic nucleoside derivatives on the growth and survival of cultured human ovarian tumor cells (line SKOV-3) and normal human lung fibroblasts was investigated. It was shown that the dialdehyde derivatives of uridine, 1--D-eritrofuranozyl uracil and 3-O--D-ribofuranosyl-2-deoxythymidine, in contrast to their unoxidized counterparts, exert marked toxic effect on SKOV-3 cells. Cultured human fibroblasts were less susceptible to the damaging effect of the dialdehyde nucleosides. The dialdehyde derivative of 1--D-eritrofuranozyl uracil demonstrated greatest differences in the cytotoxic effect on these cultures: inhibition of tumor SKOV-3 cells growth on 50% or more was achieved at the concentrations of this compound ten times lower than in the case of normal fibroblasts.

scholarly journals Colorectal Cancer Cell-Derived Small Extracellular Vesicles Educate Human Fibroblasts to Stimulate Migratory Capacity

2021 ◽  
Vol 9 ◽  
Author(s):  
Stefano Piatto Clerici ◽  
Maikel Peppelenbosch ◽  
Gwenny Fuhler ◽  
Sílvio Roberto Consonni ◽  
Carmen Veríssima Ferreira-Halder
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Tyrosine Phosphatase ◽  
Human Fibroblasts ◽  
Cell Communication ◽  
Ht29 Cells ◽  
Weight Protein ◽  
Normal Human

Colorectal cancer (CRC) is in the top 10 cancers most prevalent worldwide, affecting equally men and women. Current research on tumor-derived extracellular vesicles (EVs) suggests that these small extracellular vesicles (sEVs) play an important role in mediating cell-to-cell communication and thus potentially affecting cancer progression via multiple pathways. In the present study, we hypothesized that sEVs derived from different CRC cell lines differ in their ability to reprogram normal human fibroblasts through a process called tumor education. The sEVs derived from CRC cell lines (HT29 and HCT116) were isolated by a combination of ultrafiltration and polymeric precipitation, followed by characterization based on morphology, size, and the presence or absence of EV and non-EV markers. It was observed that the HT29 cells displayed a higher concentration of sEVs compared with HCT116 cells. For the first time, we demonstrated that HT29-derived sEVs were positive for low-molecular-weight protein tyrosine phosphatase (Lmwptp). CRC cell-derived sEVs were uptake by human fibroblasts, stimulating migratory ability via Rho-Fak signaling in co-incubated human fibroblasts. Another important finding showed that HT29 cell-derived sEVs are much more efficient in activating human fibroblasts to cancer-associated fibroblasts (CAFs). Indeed, the sEVs produced by the HT29 cells that are less responsive to a cytotoxic agent display higher efficiency in educating normal human fibroblasts by providing them advantages such as activation and migratory ability. In other words, these sEVs have an influence on the CRC microenvironment, in part, due to fibroblasts reprogramming.

scholarly journals Expression of colony-stimulating factor genes by normal human mesothelial cells and human malignant mesothelioma cells lines in vitro

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 940-946 ◽  
Author(s):  
GD Demetri ◽  
BW Zenzie ◽  
JG Rheinwald ◽  
JD Griffin
Keyword(s):  
Cell Lines ◽  
Malignant Mesothelioma ◽  
Interleukin 1 ◽  
Mesothelial Cells ◽  
Biologically Active ◽  
Northern Analysis ◽  
Early Passage ◽  
Gm Csf ◽  
Normal Human ◽  
Mesothelioma Cell

Abstract We investigated normal human mesothelial cells and human malignant mesothelioma cell lines for the ability to produce hematopoietic colony- stimulating factors (CSFs) in culture. Early passage cultures of normal diploid human mesothelial cells spontaneously expressed detectable levels of M-CSF mRNA transcripts, but lacked detectable transcripts for GM-CSF or G-CSF. Exposure of normal mesothelial cells to epidermal growth factor (EGF), lipopolysaccharide (LPS), or tumor necrosis factor (TNF) induced expression of G-CSF mRNA. The combination of EGF and TNF induced threefold more G-CSF transcripts than did either factor alone. GM-CSF transcripts were induced only by the combination of TNF and EGF. Interleukin-1 beta (IL-1 beta) transcripts were induced by EGF, TNF, or LPS and were inhibited by hydrocortisone (HC). All malignant mesothelioma cell lines tested also spontaneously expressed M-CSF transcripts. However, in contrast to normal mesothelial cells, two of four malignant mesothelioma cell lines also autonomously expressed G- CSF and GM-CSF transcripts without TNF, EGF, or LPS stimulation. Secretion of biologically active CSFs was confirmed by testing media conditioned by the various cell types examined. The detection of biologically active CSFs correlated well with the presence of detectable CSF transcripts by Northern analysis. These data indicate that (a) normal human mesothelial cells spontaneously express detectable levels of M-CSF mRNA in culture; (b) EGF is an essential cofactor for optimal induction of G-CSF and GM-CSF expression; (c) exposure of normal mesothelial cells to inflammatory mediators such as LPS and TNF increases the levels of transcripts for CSFs and IL-1 beta; and (d) as compared with normal human mesothelial cells, some cell lines of human malignant mesothelioma exhibit aberrant gene expression for multiple cytokines, including G-CSF, GM-CSF, IL-1 beta, and IL-6.

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