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Shiga toxins (Stxs) induce apoptosis in a variety of cell types. Here, we
show that Stx1 induces apoptosis in the undifferentiated myelogenous leukemia
cell line THP-1 in the absence of tumor necrosis factor alpha (TNF-alpha) or
death receptor (TNF receptor or Fas) _expression_. Caspase-8 and -3 inhibitors
blocked, and caspase-6 and -9 inhibitors partially blocked, Stx1-induced
apoptosis. Stx1 induced the mitochondrial pathway of apoptosis, as activation of
caspase-8 triggered the (i) cleavage of Bid, (ii) disruption of mitochondrial
membrane potential, and (iii) release of cytochrome c into the cytoplasm.
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