Staurosporine induces apoptosis through both caspase-dependent and caspase-independent mechanisms
TLDR
Staurosporine induces apoptotic cell death through at least two redundant parallel pathways normally coexist in L1210/S cells, however, the early cell death mechanism depending on caspase activation disguises the late casp enzyme-independent apoptotic process.Abstract:
Sensitivity of tumor cells to anticancer therapy depends on the ability of the drug to induce apoptosis. However, multiple signaling pathways control this induction and thus determine this sensitivity. We report here that staurosporine, a well known inducer of apoptosis in a wide range of cell lines, displays distinct ability to trigger apoptosis in two different L1210 sublines (termed L1210/S and L1210/0). Staurosporine treatment resulted in an early cell death (within 3 h) in L1210/S cells, while in L1210/0 cells, death occurred only after 12 h. In both instances, death occurred by apoptosis. A broad spectrum caspase inhibitor, Z-VAD-fmk, blocked early apoptosis in L1210/S cells but did not confer any protection on late apoptosis in L1210/0 cells. Protection by Z-VAD-fmk observed in L1210/S cells was not lasting and unmasked a secondary process of cell death that also exhibited characteristics of apoptosis. Thus, staurosporine induces apoptotic cell death through at least two redundant parallel pathways. These two pathways normally coexist in L1210/S cells. However, the early cell death mechanism depending on caspase activation disguises the late caspase-independent apoptotic process. Staurosporine-induced apoptosis in L1210/0 cells develops only by the caspase-independent mechanism due to a general defect in caspase activation.read more
Citations
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Astrocyte apoptosis: implications for neuroprotection.
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Staurosporine induces apoptosis of melanoma by both caspase-dependent and -independent apoptotic pathways.
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Control of mitochondrial integrity by Bcl-2 family members and caspase-independent cell death.
TL;DR: This review will focus on the regulation of mitochondrial integrity by Bcl-2 family members with particular attention to the controlled release of factors involved in caspase-independent cell death.
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ERK and cell death: ERK1/2 in neuronal death.
TL;DR: Recent evidence for a role of ERK1/2 in neuronal death is summarized and the mechanisms involved in ERK 1/2 mediating neuronal death are discussed.
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Cathepsin D mediates cytochrome c release and caspase activation in human fibroblast apoptosis induced by staurosporine.
TL;DR: Analysis of the relative sequence of apoptotic events indicates that, in this cell type, cathepsin D acts upstream of cytochrome c release and caspase activation, and implies that cytosolic cathePSin D is a key mediator in staurosporine-induced apoptosis.
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