This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Modica-Napolitano, J. S. Articles by Chen, L. B. Search for Related Content PubMed PubMed Citation Articles by Modica-Napolitano, J. S. Articles by Chen, L. B.

Aberrant Mitochondria in Two Human Colon Carcinoma Cell Lines¹

Dana-Farber Cancer Institute, Department of Surgery, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02115

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 cosiderably lower than those of CV-1 and MIP101 mitochondria (approximately 3 as compared to >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.

¹ This work has been supported by grants from the NIH (CA44704, CA19589, CA22427, GM38318).

² Supported by postdoctoral training grants from the NIH to A. B. Pardee and T. Benjamin.

Received 9/23/88. Revised 3/ 2/89. Revised 3/15/89.

This article has been cited by other articles:

				B. G. Heerdt, M. A. Houston, and L. H. Augenlicht Growth Properties of Colonic Tumor Cells Are a Function of the Intrinsic Mitochondrial Membrane Potential Cancer Res., February 1, 2006; 66(3): 1591 - 1596. [Abstract] [Full Text] [PDF]

				B. G. Heerdt, M. A. Houston, A. J. Wilson, and L. H. Augenlicht The Intrinsic Mitochondrial Membrane Potential ({Delta}{psi}m) Is Associated with Steady-State Mitochondrial Activity and the Extent to Which Colonic Epithelial Cells Undergo Butyrate-mediated Growth Arrest and Apoptosis Cancer Res., October 1, 2003; 63(19): 6311 - 6319. [Abstract] [Full Text] [PDF]

				N. Hail Jr. and R. Lotan Examining the Role of Mitochondrial Respiration in Vanilloid-Induced Apoptosis J Natl Cancer Inst, September 4, 2002; 94(17): 1281 - 1292. [Abstract] [Full Text] [PDF]

				N. Hail Jr. and R. Lotan Mitochondrial Respiration Is Uniquely Associated with the Prooxidant and Apoptotic Effects of N-(4-Hydroxyphenyl)retinamide J. Biol. Chem., November 30, 2001; 276(49): 45614 - 45621. [Abstract] [Full Text] [PDF]

				N. Hail Jr., E. M. Youssef, and R. Lotan Evidence Supporting a Role for Mitochondrial Respiration in Apoptosis Induction by the Synthetic Retinoid CD437 Cancer Res., September 1, 2001; 61(18): 6698 - 6702. [Abstract] [Full Text] [PDF]

				E. A. Lipscomb, P. D. Sarmiere, and R. S. Freeman SM-20 Is a Novel Mitochondrial Protein That Causes Caspase-dependent Cell Death in Nerve Growth Factor-dependent Neurons J. Biol. Chem., February 9, 2001; 276(7): 5085 - 5092. [Abstract] [Full Text] [PDF]