TY - JOUR
T1 - Dissociation of staurosporine-induced apoptosis from G2-M arrest in SW620 human colonic carcinoma cells
T2 - Initiation of the apoptotic cascade is associated with elevation of the mitochondrial membrane potential (Δψ(m))
AU - Heerdt, B. G.
AU - Houston, M. A.
AU - Mariadason, J. M.
AU - Augenlicht, L. H.
PY - 2000/12/1
Y1 - 2000/12/1
N2 - We have identified an alternative apoptotic cascade induced in SW620 human colonic carcinoma cells by the protein kinase antagonist staurosporine (stsp). Consistent with its effect in other colonic epithelial cells, stsp induced G2-M arrest and apoptosis of SW620 cells. However, despite the paradigm that growth arrest triggers apoptotic cascades, apoptosis was detected before G2-M arrest. Reports have linked dissipation of the mitochondrial membrane potential (Δψ(m)) to the initiation of apoptosis and have linked elevation of the Δψ(m) to the escape from apoptosis. However, neither apoptosis nor cell cycle arrest were altered by the collapse of the Δψ(m), and increased Δψ(m) enhanced the initiation of apoptosis but blocked G2-M arrest. Although reactive oxygen species (ROS) have been implicated in some colonic epithelial cell and stsp-induced cascades, neither antioxidants nor the inhibition of RNA or protein synthesis altered apoptosis of SW620 cells. Finally, cytosolic cytochrome c has been linked to activation of caspase-3 and dissipation of the Δψ(m). However, caspase-3 activation preceded the accumulation of cytochrome c in the cytosol and was accompanied by transient elevations in both the Δψ(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 Δψ(m), ROS production, or synthesis of de novo RNA or protein, and we have linked its efficient initiation to early elevation of the Δψ(m).
AB - We have identified an alternative apoptotic cascade induced in SW620 human colonic carcinoma cells by the protein kinase antagonist staurosporine (stsp). Consistent with its effect in other colonic epithelial cells, stsp induced G2-M arrest and apoptosis of SW620 cells. However, despite the paradigm that growth arrest triggers apoptotic cascades, apoptosis was detected before G2-M arrest. Reports have linked dissipation of the mitochondrial membrane potential (Δψ(m)) to the initiation of apoptosis and have linked elevation of the Δψ(m) to the escape from apoptosis. However, neither apoptosis nor cell cycle arrest were altered by the collapse of the Δψ(m), and increased Δψ(m) enhanced the initiation of apoptosis but blocked G2-M arrest. Although reactive oxygen species (ROS) have been implicated in some colonic epithelial cell and stsp-induced cascades, neither antioxidants nor the inhibition of RNA or protein synthesis altered apoptosis of SW620 cells. Finally, cytosolic cytochrome c has been linked to activation of caspase-3 and dissipation of the Δψ(m). However, caspase-3 activation preceded the accumulation of cytochrome c in the cytosol and was accompanied by transient elevations in both the Δψ(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 Δψ(m), ROS production, or synthesis of de novo RNA or protein, and we have linked its efficient initiation to early elevation of the Δψ(m).
UR - http://www.scopus.com/inward/record.url?scp=0034541212&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034541212&partnerID=8YFLogxK
M3 - Article
C2 - 11118056
AN - SCOPUS:0034541212
SN - 0008-5472
VL - 60
SP - 6704
EP - 6713
JO - Cancer research
JF - Cancer research
IS - 23
ER -