The intrinsic mitochondrial membrane potential of colonic carcinoma cells is linked to the probability of tumor progression

We subcloned cell lines from SW620 cells establishing that, despite the dynamic nature of the mitochondrial membrane potential (Δψ _m), there are significant and stable differences in the intrinsic Δψ_m among cells within an in vitro population of human colonic carcinoma cells. Whereas more dramatic differences in Δψ_m would likely perturb essential mitochondrial functions, the differences in Δψ_m of the subclones did not affect steady-state reactive oxygen species levels, electron transport activity, or cellular viability and growth rates. However, the differences in intrinsic Δψ_m had a significant effect on the tumorigenic behavior of the cells. Subcloned cell lines with higher Δψ_m were more likely to exhibit elevated steady-state levels of vascular endothelial growth factor and matrix metalloproteinase 7, and increased invasive behavior (properties associated with tumor progression), than cells with lower intrinsic Δψ_m, whereas cells with lower Δψ_m were more likely to respond to the chemopreventive activities of butyrate, including Δψ_m dissipation, growth arrest, and apoptosis, than cells with higher Δψ_m. Therefore, these data establish that the probability for tumor development and progression is linked to stable differences in the intrinsic Δψ_m of colonic epithelial cells.