Author/Authors :
Don، نويسنده , , Anthony S and Kisker، نويسنده , , Oliver and Dilda، نويسنده , , Pierre and Donoghue، نويسنده , , Neil and Zhao، نويسنده , , Xueyun and Decollogne، نويسنده , , Stephanie and Creighton، نويسنده , , Belinda and Flynn، نويسنده , , Evelyn and Folkman، نويسنده , , Judah and Hogg، نويسنده , , Philip J، نويسنده ,
Abstract :
Mitochondria are the powerhouse of the cell and their disruption leads to cell death. We have used a peptide trivalent arsenical, 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO), to inactivate the adenine nucleotide translocator (ANT) that exchanges matrix ATP for cytosolic ADP across the inner mitochondrial membrane and is the key component of the mitochondrial permeability transition pore (MPTP). GSAO triggered Ca2+-dependent MPTP opening by crosslinking Cys160 and Cys257 of ANT. GSAO treatment caused a concentration-dependent increase in superoxide levels, ATP depletion, mitochondrial depolarization, and apoptosis in proliferating, but not growth-quiescent, endothelial cells. Endothelial cell proliferation drives new blood vessel formation, or angiogenesis. GSAO inhibited angiogenesis in the chick chorioallantoic membrane and in solid tumors in mice. Consequently, GSAO inhibited tumor growth in mice with no apparent toxicity at efficacious doses.
