Basis of differential cytotoxicity exhibited by rhodamine 123 for certain carcinoma cell types

The authors have previously demonstrated the inhibitory effect of rhodamine 123 (Rh123) on mitochondrial bioenergetic function and established mitochondrial F1-F0 ATPase as the primary target site for Rh123 toxicity. Further, they found that the amount of Rh123 taken up by isolated rat liver mitochondria is a linear function of mitochondrial membrane potential. Here they investigated the possibility that the differential cytotoxicity exhibited by Rh123 for certain carcinoma cell types might be a function of an increased mitochondrial membrane potential. Membrane potential in mitochondria isolated from cultured cells was measured by equilibrium distribution of 86Rb. Mitochondria from CX-1, a Rh123-sensitive carcinoma cell type, had a higher membrane potential (163 +/- 7mV) than did mitochondria from CV-1, a Rh123-insensitive, normal epithelial cell type (104 +/- 9mV). In addition polarographic determination of respiratory activity of mitochondria isolated from these cells showed that CX-1 mitochondria were more sensitive than CV-1 mitochondria to inhibition by Rh123. Finally, there was no evidence of differential sensitivity of F1-F0 ATPase activity to Rh123 in CX-1 vs. CV-1 mitochondria. These data strongly suggest that inherent differences in mitochondrial membrane potential contribute to the differential cytotoxicity exhibited by Rh123 for certain carcinoma cell types