Apoptosis Biochemical events and relevance to cancer chemotherapy

Şen, Sinan; D’Incalci, Maurizio

doi:10.1016/0014-5793(92)80914-3

Cited by 227 publications

(113 citation statements)

References 77 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…30,31 To analyze the pattern of death induction by different stimuli in the same cell line, we have performed a set of experiments on HeLa cells induced to die by two ways: (i) etoposide administration, which is widely described apoptogenic treatment 32,33 and (ii) long term-culture. 34,35 Microscopical observation indicated that, during apoptosis induction by different ways, cells tend to detach from the solid support, to float in the medium and to show typical apoptotic markers.…”

Section: Discussionmentioning

confidence: 99%

Differential involvement of DNases in HeLa cell apoptosis induced by etoposide and long term-culture

et al. 1999

View full text Add to dashboard Cite

We have applied to human HeLa cells two different stimuli of apoptosis: the antitumoral drug etoposide, and a morè physiological' death condition, obtained by growing cells in the same medium for long time periods, for up to 10 days. Analysis of different parameters demonstrated that in both experimental systems the same apoptotic features are visible. However, the DNA degradation pattern appeared to be different, suggesting the involvement of different DNases. In this view, we have analyzed the activity and expression of Ca 2+ -Mg 2+ -dependent and acid DNases. We have observed that DNase I is not modulated during apoptosis. In contrast, the acid L-DNase II (derived from Leukocyte Elastase Inhibitor by post-translational modification), recently identified in our laboratory, is mainly active in the apoptotic pathway induced by long term-culture. Furthermore, we have provided evidence that while caspase 3 is activated by both inducers, caspase 1 is essential only for the etoposide-induced apoptosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential involvement of DNases in HeLa cell apoptosis induced by etoposide and long term-culture

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Apoptosis, programmed cell death, is accompanied by increased intracellular Ca2+, leading to the activation of a Ca2+-dependent endonuclease (Sen and D'Incalci, 1992), and by increased expression of transglutaminase, thought to be responsible for transformation of the cells into insoluble condensed apoptotic bodies . In such situations intracellular PAI-2 could be polymerized.…”

Section: Discussionmentioning

confidence: 99%

Type‐2 plasminogen‐activator inhibitor is a substrate for trophoblast transglutaminase and Factor XIII_a

Jensen

Lóránd

Ebbesen

et al. 1993

European Journal of Biochemistry

View full text Add to dashboard Cite

Plasminogen‐activator inhibitor type‐2 (PAI‐2), a serine‐proteinase inhibitor, suppresses fibrinolysis by blocking both urokinase and tissue‐type plasminogen activators. The 43‐kDa PAI‐2 molecule is an abundant cytosolic protein in certain cell types, but can upon appropriate stimulation be secreted as an approximately 60–70‐kDa glycoprotein. However, in trophoblast membranes PAI‐2 activity is associated with large covalent complexes (Jensen, P. H., Nykjær, P., Andreasen P. A., Lund, L., Åstedt, B. Lecander, I. & Gliemann, J. (1989) Biochim. Biophys. Acta 986, 135–140). This study shows that PAI‐2 can act as a substrate for both tissue transglutaminase and activated plasma factor XIII. In the presence of Ca2+, either of these will catalyze the incorporation of primary amines, such as putrescine, into PAI‐2. Moreover, in reactions with tissue transglutaminase, PAI‐2 homopolymers and, in conjunction with other biological substrates, heteropolymers were observed. As judged by the test of incorporating 125I‐urokinase into SDS‐resistant 125I‐urokinase/PAI‐2 complexes, polymerized PAI‐2 retained its inhibitory activity. Furthermore, syncytiotrophoblast microvillous membranes and trophoblast detergent extracts incorporated 125I‐PAI‐2 into large structures in a reaction inhibited by putrescine and a synthetic inhibitor of transglutaminase. Trophoblast transglutaminase was identified as a tissue transglutaminase by non‐denaturing gel electrophoresis and dansylcadaverine activity staining, fibronectin binding and Western blotting with a specific antibody. The transglutaminase‐catalyzed and Ca2+‐dependent anchoring of PAI‐2 to extracellular membrane structures might have the purpose of focally regulating fibrinolysis.

show abstract

“…In apoptosis, cell death is slow and occurs long after DNA degradation, the condensation of chromatin and its marginalisation at the edges of the nuclear membrane (Duvall & Wyllie, 1986;Arends et al, 1990). Although apoptosis is a common event seen during normal embryonic development and tissue renewal, it can also occur after major perturbations in vital cellular processes caused by cytotoxic chemical agents (Barry et al, 1991;Sen & D'Incalci, 1992).…”

Section: Discussionmentioning

confidence: 99%

Caffeine potentiates the lethality of tumour necrosis factor in cancer cells

Belizário

Tilly²,

Sherwood³

1993

Br J Cancer

View full text Add to dashboard Cite

Summary In this study we have investigated the interaction of caffeine, a prototypic methylxanthine, and TNF on the induction of cell death in mouse and human cell lines during progression from G, to successive phases of the cell cycle. Exposure of cells to TNF (0.1-100 ng ml-) as single agent for 48 h caused low or no lethality. The rates of cell death increased significantly when cells cultured with TNF for 24 h were exposed to caffeine (2.5-20 mM). The magnitude of the enhancement by caffeine was TNF and caffeine dose-dependent. The most effective response to this combination was observed in the mouse cell lines, WEHI and L929, followed by the human cell lines, HeLa, A375 and MCF-7, respectively. In L929 cells, TNF treatment did not inhibit DNA synthesis during the first S phase of the cell cycle (20-24 h), but it did block the progress toward a second S phase, indicating the cells were arrested at G2 phase or mitosis. Caffeine had great enhancer effect on L929 cells exposed to TNF for 24 h, but the effect was reduced in cells with either less than 24 h or greater than 28 h of exposure. L929 cells stimulated with TNF died via apoptosis, as judged by both morphological criteria and the occurrence of internucleosomal DNA cleavage. Exposure of TNF-treated cells to caffeine caused a greater increase in the proportion of apoptotic cells as well as the extent of internucleosomal DNA fragmentation.

show abstract

Apoptosis Biochemical events and relevance to cancer chemotherapy

Cited by 227 publications

References 77 publications

Differential involvement of DNases in HeLa cell apoptosis induced by etoposide and long term-culture

Differential involvement of DNases in HeLa cell apoptosis induced by etoposide and long term-culture

Type‐2 plasminogen‐activator inhibitor is a substrate for trophoblast transglutaminase and Factor XIII_a

Caffeine potentiates the lethality of tumour necrosis factor in cancer cells

Contact Info

Product

Resources

About

Apoptosis Biochemical events and relevance to cancer chemotherapy

Cited by 227 publications

References 77 publications

Differential involvement of DNases in HeLa cell apoptosis induced by etoposide and long term-culture

Differential involvement of DNases in HeLa cell apoptosis induced by etoposide and long term-culture

Type‐2 plasminogen‐activator inhibitor is a substrate for trophoblast transglutaminase and Factor XIIIa

Caffeine potentiates the lethality of tumour necrosis factor in cancer cells

Contact Info

Product

Resources

About

Type‐2 plasminogen‐activator inhibitor is a substrate for trophoblast transglutaminase and Factor XIII_a