Dissociation of staurosporine-induced apoptosis from G(2)-M arrest in SW620 human colonic carcinoma cells: Initiation of the apoptotic cascade is associated with elevation of the mitochondrial membrane potential (Delta psi(m))

We have identified an alternative apoptotic cascade induced in SW620 human colonic carcinoma cells by the protein kinase antagonist staurosporine (sts p). Consistent with its effect in other colonic epithelial cells, stsp indu ced G(2)-M arrest and apoptosis of SW620 cells. However, despite the paradi gm that growth arrest triggers apoptotic cascades, apoptosis was detected b efore G(2)-M arrest. Reports have linked dissipation of the mitochondrial m embrane potential (Delta psi (m)) to the initiation of apoptosis and have l inked elevation of the Delta psi (m) to the escape from apoptosis. However, neither apoptosis nor cell cycle arrest were altered by the collapse of th e Delta psi (m), and increased Delta psi (m), enhanced the initiation of ap optosis but blocked G(2)-M arrest. Although reactive oxygen species (ROS) h ave been implicated in some colonic epithelial cell and stsp-induced cascad es, neither antioxidants nor the inhibition of RNA or protein synthesis alt ered apoptosis of SW620 cells. Finally, cytosolic cytochrome c has been lin ked to activation of caspase-1 and dissipation of the Delta psi (m). Howeve r, caspase-3 activation preceded the accumulation of cytochrome c in the cy tosol and was accompanied by transient elevations in both the Delta psi (m) and mitochondria-associated cytochrome c. Therefore, we have identified a distinct apoptotic cascade in SW620 cells that was induced independently of growth arrest, dissipation of the Delta psi (m), ROS production, or synthe sis of de novo RNA or protein, and we have linked its efficient initiation to early elevation of the Delta psi (m).