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 (Deltapsim), there are significant and stable differences in the intrinsic Deltapsim among cells within an in vitro population of human colonic carcinoma cells. Whereas more dramatic differences in Deltapsim would likely perturb essential mitochondrial functions, the differences in Deltapsim 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 Deltapsim had a significant effect on the tumorigenic behavior of the cells. Subcloned cell lines with higher Deltapsim 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 Deltapsim, whereas cells with lower Deltapsim were more likely to respond to the chemopreventive activities of butyrate, including Deltapsim dissipation, growth arrest, and apoptosis, than cells with higher Deltapsim. Therefore, these data establish that the probability for tumor development and progression is linked to stable differences in the intrinsic Deltapsim of colonic epithelial cells.
Heerdt
Barbara G
BG
Department of Oncology, Albert Einstein Cancer Center, Montefiore Medical Center, Bronx, New York 10467, USA. heerdt@aecom.yu.edu
Houston
Michele A
MA
Augenlicht
Leonard H
LH
D002087:Butyrates / Q000494:pharmacology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D003110:Colonic Neoplasms / Q000473:pathology* / Q000648:ultrastructure*; D018450:Disease Progression; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*
D002087:Butyrates