Abstract
Alterations in the biochemistry of mitochondria have been associated with cell transformation and the acquisition of drug resistance to certain chemotherapeutic agents, suggesting that mitochondria may play a supportive role for the cancer cell phenotype. Mitochondria are multifunctional organelles that contribute to the cellular adenosine triphosphate (ATP) pool and cellular redox balance through the production of reactive oxygen intermediates (ROI). Our laboratory has focused on these mitochondrial functions in the context of cancer cell physiology to evaluate the potential role of mitochondria as controllers of tumour cell proliferation. Low concentrations of ROI have been implicated as messengers in intracellular signal transduction mechanisms; thus an imbalance of ROI production from the mitochondria may support cancer cell growth. In addition, suppression of mitochondrial ATP production can halt cell cycle progression at two energetic checkpoints, suggesting that the use of tumor-selective agents to reduce ATP production may offer a therapeutic target for cancer growth control.
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REFERENCES
Andrews, P. A., and Albright, K. D. (1992). Cancer Res. 52, 1895–1901.
Bernal, S. D., Lampidis, T. J., McIsaac, R. M., and Chen, L. B. (1983). Science. 222, 169–172.
Biggs, J. R., and Kraft, A. S. (1995). J. Mol. Med. 73, 509–514.
Boveris, A., Oshino, N., and Chance, B. (1972). Biochem. J. 128, 617–630.
Brightman, A. O., Wang, J., Kin-man Miu, R., Sun, I. L., Barr, R., Crane, F. L., and Morre, D. J. (1992). Biochim. Biophys. Acta 1105, 109–117.
Burdon, R. H. (1995). Free Rad. Biol. Med. 18, 775–794.
Chance, B., Sies, H., and Boveris, A. (1979). Physiol. Rev. 59, 527–605.
Chen, L. B. (1988). Annu. Rev. Cell Biol. 4, 155–181.
Christman, J. E., Miller, D. S., Coward, P., Smith, L. H., and Teng, N. N. (1990). Gynecol. Oncol. 39, 72–79.
Derman, A. I., Prinz, W. A., Belin, D., and Beckwith, J., (1993). Science 262, 1744–1747.
Dorward, A. M., and Singh, G. (1996). Anticancer Res. 16, 443–447.
Guyton, K. Z., Liu, Y., Gorospe, M., Xu, Q., and Holbrook, N. J. (1996). J. Biol. Chem. 271, 4138–4142.
Henderson, B. W., and Dougherty, T. J. (1992). Photochem. Photobiol. 55, 145–157.
Herr, H. W., Huffman, J. L., Huryk, R., Heston, W. D. W., Melamed, M. R., and Whitmore, Jr., W. F. (1988). Cancer Res. 48, 2061–2063.
Hwang, C., Sinskey, A. J., and Lodish, H. F. (1992). Science 257, 1496–1502.
Kariya, K., Nakamura, K., Nomoto, K., Kobayashi, Y., and Namiki, M. (1995). Cancer Biother. 10, 139–145.
Knebel, A., Rahmsdorf, H.J., Ullrich, A., and Herrlich, P. (1996). EMBO J. 15, 5314–5325.
Koya, K., Li, Y., Wang, H., Ukai, T., Tatsuta, N., Kawakami, M., Shishido, T., and Chen, L. B. (1996). Cancer Res. 56, 538–543.
Krag, D. N., Theon, A. P., Gan, L., Wardell, J., and Tao, S. Z. (1989). J. Surg. Res. 46, 361–365.
Lampidis, T. J., Bernal, S. D., Summerhayes, I. C., and Chen, L. B. (1983). Cancer Res. 43, 716–720.
MacLachlan, T. K., Sang, N., and Giordano, A. (1995). Crit. Rev. Eukaryot. Gene Expr. 5, 127–156.
Matsushime, H., Roussel, M. F., Ashmun, R., and Sherr, C. J. (1991). Cell 65, 701–713.
Meier, B., Jesaitis, A. J., Emmendorffer, A., Roesler, J. and Quinn, M. T. (1993). Biochem J. 289, 481–486.
Modica-Napolitano, J. S., Weiss, M. J., Chen, L. B., and Aprille, J. R. (1984). Biochem. Biophys. Res. Commun. 118, 717–723.
Modica-Napolitano, J. S., Koya, K., Weisberg, E., Brunelli, B. T., Li, Y., and Chen, L. B. (1996). Cancer Res. 56, 544–550.
Moorehead, R. A., and Singh, G. (1995). Cell. Pharmacol. 2, 311–317.
Moorehead, R. A., Armstrong, S. G., Wilson, B. C., and Singh, G. (1994). Cancer Res. 54, 2556–2559.
Murell, G. A. C., Francis, M. J. O., and Bromley, L. (1990). Biochem. J. 265, 659–665.
Ohtsubo, M., and Roberts, J. M. (1993). Science 259, 1908–1912.
Powis, G., Briehl, M., and Oblong, J. (1995). Pharmacol. Ther. 68, 149–173.
Rahn, C. A., Bombick, D. W., and Doolittle, D. J. (1991). Fund. Appl. Toxicol. 16, 435–448.
Rao, G. N. (1996). Oncogene 13, 713–719.
Resnitsky, D., Gosser, M., Bujard, H., Reed, S. I. (1994). Mol. Cell. Biol. 14, 1669–16790.
Salet, C., and Moreno, G. (1990). J. Photochem. Photobiol. 5, 133–150.
Sharkey, S. M., Wilson, B. C., Moorehead, R., and Singh, G. (1993). Cancer Res. 53, 4994–4999.
Singh, G., and Moorehead, R. (1992). Int. J. Oncol. 1, 825–829.
Singh, G., and Shaughnessy, S. G. (1988). Can. J. Physiol. Pharmacol. 66, 243–245.
Steichen, J. D., Weiss, M. J., Elmaleh, D. R., and Martuza, R. L. (1991). J. Neurosurg. 74, 116–122.
Sullivan, S. G., Chiu, D., T-Y., Errasfa, M., Wang, J. M., Qi, J-S, and Stern, A. (1994). Free Rad. Biol. Med. 16, 399–403.
Sundaresan, M., Yu, Z-X., Ferrans, V. J., Irani, K., and Finkel, T. (1995). Science 270, 296–299.
Sweet, S., and Singh, G. (1995). Cancer Res. 55, 5164–5267.
Szatrowski, T. P., and Nathan, C. F. (1991). Cancer Res. 51, 794–798.
Thannickal, V. J. and Fanburg, B. L. (1995). J. Biol. Chem. 270, 30334–30338.
van Hillegersberg, R., Kort, W. J., and Wilson, J. H. P. (1994). Drugs 48, 510–527.
Weinberg, R. A. (1995). Cell 81, 323–330.
Weisberg, E. L., Koya, K., Modica-Napolitano, J., Li, Y., and Chen, L. B. (1996). Cancer Res. 56, 551–555.
Weiss, M. J., Wong, J. R., Ha, C. S., Bleday, R., Salem, R. R., Steele, G. D., and Chen, J. B. (1987). Proc. Natl. Acad. Sci. USA 84, 5444–5448.
Wolin, M. S. (1996). Microcirculation 3, 1–17.
Zinkewich-Peotti, K., and Andrews, P. A. (1992a). Proc. Am. Assoc. Cancer Res. 33, ABS 537.
Zinkewich-Peotti, K., and Andrews, P. A. (1992b). Cancer Res. 52, 1902–1906.
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Dorward, A., Sweet, S., Moorehead, R. et al. Mitochondrial Contributions to Cancer Cell Physiology: Redox Balance, Cell Cycle, and Drug Resistance. J Bioenerg Biomembr 29, 385–392 (1997). https://doi.org/10.1023/A:1022454932269
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DOI: https://doi.org/10.1023/A:1022454932269