The Protein Kinase Inhibitor Staurosporine Induces Morphological Changes Typical of Apoptosis in MOLT-4 Cells without Concomitant DNA Fragmentation

Influence of Bcl-2 overexpression on the ceramide pathway in daunorubicin-induced apoptosis of leukemic cells

“…However, we could only detect smears in BL cells treated with DNR, in multiple experiments. The di culty to observe DNA laddering in lymphoid cell lines has been reported, and it appears not to be an absolute requirement in the de®nition of apoptosis (Catchpoole and Stewart, 1993;Falcieri et al, 1993;Fisher et al, 1993). In addition, ®eld inversion gel electrophoresis allowed us to observe DNA macrofragments of 50 ± 150 kbp in both HL60 and BL cells, as previously described for epithelial cells (Oberhammer et al, 1993), thymocytes (Brown et al, 1993;Walker et al, 1991), and leukemic cells (Huang et al, 1995;QuilletMary et al, 1996) undergoing apoptosis induced by various agents.…”

Caspase-activated DNase Is Necessary and Sufficient for Oligonucleosomal DNA Breakdown, but Not for Chromatin Disassembly during Caspase-dependent Apoptosis of LN-18 Glioblastoma Cells

“…IMR-5, IMR-32, and LAI-5S cells) (18,23,27); and third, cells showing stage II nuclear morphology but not oligonucleosomal DNA breakdown (e.g. MOLT-4 and SK-N-AS cells) (21,23). In all cases, cells need functional DFF40/CAD to display both hallmarks after caspase activation.…”

Drug-induced death of leukaemic cells after G2/M arrest: higher order DNA fragmentation as an indicator of mechanism

“…In common with many of the other biological parameters studied, staining of CEM or MOLT-4 cells exposed to etoposide over a wide concentration range indicated two response patterns. (Barres et al, 1992;Oberhammer et al, 1922), and specifically including cytotoxic drugs in some situations (Bertrand et al, 1991;Hotz et al, 1992; Catchpoole and Stewart, 1993;Falcieri et al, 1993). Although it is generally accepted that cytotoxic drugs elicit apoptosis via a 'final common pathway', there have been few molecular criteria apart from DNA ladders to characterize this process (Lennon et al, 1991;Marks and Fox, 1991 Figure 2F) and a commensurate decrease in cell number, 0.5 gM etoposide caused a cytostatic effect (Figure 1).…”

“…As MOLT-4 cells were significant in demonstrating the limitations of DNA ladders as a molecular indicator of apoptosis (Hotz et al, 1992;Catchpoole and Stewart, 1993;Falcieri et al, 1993), detection of higher-order fragmentation in these cells after exposure to etoposide is noteworthy. Such a result was reported by Beere et al (1995) using 50 gM etoposide.…”

“…However, the biological significance accorded to internucleosomal fragmentation of DNA is changing from the perception of an early indicator (Barry and Eastman, 1992;Smith et al, 1992), to a molecular change concurrent with morphological evidence of cell death (Lazebnik et al, 1995) and denoted by Vaux and Strasser (1996) as a 'post-mortem' event. Moreover, some cell populations do not exhibit ladders after drug treatment (Bertrand et al, 1991;Hotz et al, 1992;Falcieri et al, 1993). Other studies, however, indicate the absence of ladders when cell death is not immediate, but, in response to lesser concentrations, occurs 24 h tional p53 (Lowe et al, 1993), and the role of this gene in mediating drug-induced apoptosis is clear and has been implicated in determining response to therapy (Lowe et al, 1994;Eliopoulos et al, 1995;Rusch et al, 1995;Marks et al, 1996).…”