Aberrant mitochondria in two human colon carcinoma cell lines.
Electron micrographs of CCL237 and FET cells (two slowly growing, differentiated human colon carcinoma lines) revealed enlarged mitochondria with few cristae. Polarographic measurement of respiratory activity in mitochondria isolated from these cell lines was compared to that of CV-1 cells (a normal monkey kidney epithelial line) and MIP101 cells (another human colon carcinoma line), both of which have mitochondria with a "normal" appearance. The respiratory control ratios of CCL237 and FET mitochondria were found to be considerably lower than those of CV-1 and MIP101 mitochondria (approximately 3 as compared to greater than 10, respectively), indicating that in CCL237 and FET mitochondria the processes of substrate oxidation and phosphorylation of ADP are only loosely coupled. In intact cells, differences in radiolabeled tetraphenylphosphonium uptake showed that the mitochondrial membrane potential in CCL237 and FET cells was less than that in CV-1 and MIP101 cells, and that nigericin failed to hyperpolarize the mitochondria of CCL237 and FET cells. In addition, FET mitochondria exhibited significantly lower ADP-stimulated and uncoupled respiratory rates than mitochondria isolated from the other cell types, indicating that in the former, the capacity for oxidative phosphorylation is somehow impaired. Selective toxicity of FET cells was obtained by treatment with 2-deoxyglucose, an inhibitor of glycolysis, suggesting the possibility of exploiting the phenotype of impaired oxidative metabolism for chemotherapy.
Modica-Napolitano
J S
JS
Dana-Farber Cancer Institute, Department of Surgery, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Steele
G D
GD
Chen
L B
LB
D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000473:pathology / Q000648:ultrastructure*; D003847:Deoxyglucose / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure*; D009861:Onium Compounds / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D010101:Oxygen Consumption
D009861:Onium Compounds; D009943:Organophosphorus Compounds; D003847:Deoxyglucose; C013289:tetraphenylphosphonium