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S Verhaegen

Publications and source records attributed to S Verhaegen.

9 recordsLinked to original sources
PubMed1995

Inhibition of apoptosis by antioxidants in the human HL-60 leukemia cell line.

Cell death via apoptosis is an important event involved in a number of immunological processes. Recently, apoptosis has been associated with oxidative stress in a number of cell systems. Here we assessed the inhibitory capacity of different antioxidants on UV- and drug-induced apoptosis in the human leukemic cell line, HL-60. We found that the oxygen radical scavenger, BHA, the radioprotector cysteamine and the metal chelators, pyrrolidinedithiocarbamate (PDTC), diethyldithiocarbamate (DEDTC), and dimethyldithiocarbamate (DMDTC), were able to significantly inhibit nuclear fragmentation and reduce the formation of apoptotic bodies in UV-irradiated human leukemic cells. Both BHA and PDTC were found to reduce DNA fragmentation as assessed by in situ DNA nick-end labelling and quantification thereof using fluorescence flow cytometry. In addition to inhibiting UV-induced apoptosis, PDTC was also capable of reducing the amount of apoptosis induced by a range of cytotoxic drugs, such as actinomycin-D, camptothecin, etoposide, and melphalan, whereas BHA and cysteamine were not as effective in these cases after more than four hours in culture when compared to PDTC. To further elucidate the working mechanism of PDTC, we have looked at the effect of PDTC on DNA fragmentation in isolated nuclei, under conditions that promote activation of endogenous endonuclease involved in apoptosis. In contrast to ZnCl2, a potent inhibitor of endonuclease activity, PDTC was unable to inhibit DNA-ladder formation in this assay. Taken together, these results indicate that oxygen radicals may have a central role to play in the induction of apoptosis and that dithiocarbamates can serve as potent inhibitors of apoptosis induced by a wide variety of stimuli.

Antioxidants↗
PubMed1994

Zinc inhibits UV radiation-induced apoptosis but fails to prevent subsequent cell death.

Zinc ions inhibit the morphological and DNA fragmentation features of apoptosis in a number of systems. HL-60 cells pretreated with zinc and exposed to UV irradiation maintained their normal morphology for up to 8 h, whereas non-zinc-treated cells underwent extensive apoptosis. Zinc pretreatment also inhibited both single and double-stranded DNA fragmentation, which is characteristic of apoptosis. The most effective zinc concentration that blocked apoptosis over short incubation periods (up to 8 h) was also the most toxic over extended time periods (> or = 12 h). The mechanism of cell death at these longer time periods was akin to necrosis, but occurred in the absence of any DNA fragmentation. The effects of the nuclease inhibitor aurintricarboxylic acid (ATA) was also examined on UV-induced apoptosis in HL-60 cells. ATA had no toxic effects over the concentration range tested, but also failed to prevent DNA fragmentation in whole cells. Further analysis showed that it effectively inhibited DNA fragmentation in isolated nuclei.

Apoptosis↗
PubMed1989

Suggestive evidence that genes controlling invasion and metastasis of T-cell lymphomas are located on mouse chromosome 3.

Cell lines differing in their malignant potential have been derived from the murine BW5147 T-cell lymphosarcoma. To evaluate the involvement of chromosomal aberrations in tumor progression within this model, we have analyzed the karyotypes and the in vitro invasiveness of 13 related nonmetastatic and metastatic variants. Giemsa banding revealed the presence of several marker chromosomes, one of which was of particular importance. Depending on the cell line, four variants of this marker I were found: Marker Ia corresponds to two translocated chromosomes 3, marker Ib is a deleted Ia marker, marker Ic is a Ib translocated to small unidentified chromosome fragment, and marker Id is a further deleted Ib marker. The Ia and Id markers were characteristic for the noninvasive, nonmetastatic lines, whereas the Ib and Ic markers predominated in the invasive, metastatic variants. The results suggest that metastasis-enhancing genes are located between the D and FI band of mouse chromosome 3 and that metastasis-suppressing genes are located between the FI and H band of the same chromosome.

Animals↗
PubMed1989

The in vitro invasive behavior of human myelomonocytic cell lines is modulated by HuIFN-gamma and pertussis toxin.

Using an in vitro monolayer invasion assay (MIA), we analyzed the interaction of human myeloid cell lines representing different maturation stages with murine fibroblastic monolayers. After 24 h of coculture, only promonocytic U937 cells invaded the monolayer to an appreciable extent in contrast to less-differentiated KG1a, KG1, and HL-60 cells and more mature THP-1 cells. Human interferon-gamma (HuIFN-gamma) treatment was found to induce maturation in the U937 line and resulted in a considerable reduction of interaction with the monolayer. Thus, the capacity of myeloid cells to interact with a fibroblastic monolayer is restricted to a specific maturation stage. Interaction of U937 cells was also abolished when they were treated with pertussis toxin (PT), an agent known to induce monocytosis in vivo, indicating that the MIA may serve as an in vitro simulation of the extravasation of blood borne cells. Finally, although both HuIFN-gamma and PT are able to block cell spreading in the MIA, no effect could be seen on the capacity of U937 cells to phagocytose.

Humans↗
PubMedDate not supplied

Interaction of B-cell hybridomas with fibroblast or hepatocyte monolayers in vitro and their metastatic behaviour in vivo.

Using an in vitro monolayer assay (MIA) we analyzed the invasive behaviour of a panel of B-cell hybridomas prepared by the fusion of non-invasive, non-metastatic NSO plasmacytoma cells and normal murine B-cells. Interaction of these hybridomas with fibroblast-like monolayers consisted mostly of adhesion on top of the monolayers, whereas only a fraction of these cells penetrated through the monolayer. This is in sharp contrast with the highly invasive properties displayed by T-cell hybridomas. Whereas T-cell hybridomas highly infiltrated monolayers of rat hepatocyte in vitro, B-cell hybridomas neither adhered to nor infiltrated hepatocyte monolayers. We found a good correlation between the degree of adhesion of B-cell hybridomas to fibroblast-like monolayers and their metastatic capabilities upon i.v. injection into syngeneic animals. Unlike T-cell hybridomas which formed diffuse metastasis in liver and spleen, B-cell hybridomas generated nodular metastatic lesions. . When normal LPS-stimulated B-lymphocytes were tested in the fibroblast-MIA, only part of the population infiltrated the monolayers. This again contrasts with T-lymphocytes where a majority of the cells penetrated through the monolayers. These results suggest that (i) B-lymphocytes express invasive properties, albeit to a lesser extent than T-lymphocytes, (ii) non-invasive B-lymphoma cells can acquire invasiveness following cell fusion with a normal B-cell, (iii) these invasive properties contribute to the malignancy of the hybridomas when tested in recipient animals.

Animals↗
PubMedDate not supplied

Membrane changes associated with the early stages of apoptosis in HEp-2 cells decrease susceptibility to adherence by Candida albicans.

The aim of the present work was to establish whether apoptotic HEp-2 cells demonstrated an altered susceptibility to adherence by the pathogenic yeast Candida albicans. Cultures of HEp-2 cells were treated with concentrations of three chemotherapeutic agents sufficient to induce cell death by apoptosis and this was confirmed by microscopic examination and by the loss of membrane asymmetry (as indicated by phosphatidylserine externalization) and the fragmentation of nuclear DNA into distinct subunits. Cells in the early stages of apoptosis demonstrated a reduced susceptibility to adherence by a number of strains of C. albicans. A correlation between the decrease in yeast adherence and the loss of membrane asymmetry, associated with the early stages of apoptosis, was established.

Annexin A5↗
PubMedDate not supplied

Experimental analysis of the metastatic phenotype of malignant leukocytes.

The metastatic phenotype (M+) is determined by the expression of the invasive (I+) and growth (G+) phenotypes at various sites along the metastatic pathway. The G, I and M phenotypes are not confined to tumor cells and may be expressed by normal cells, such as leukocytes, under certain physiological conditions. The study of the I and M phenotypes of leukocytes may yield valuable information on common mechanisms, underlying invasion and metastasis of normal and malignant cells. In this review we summarize experimental approaches that were developed for the analysis of the I and M phenotypes of normal and malignant leukocytes.

Animals↗