A novel mitochondriotoxic small molecule that selectively inhibits tumor cell growth

Cancer Cell

Volumn 2, Issue 1, 2002, Pages 29-42

  Fantin, Valeria R ^a,c   Berardi, Marcelo J ^b   Scorrano, Luca ^a   Korsmeyer, Stanley J ^a,c   Leder, Philip ^a,c  

^a HARVARD MEDICAL SCHOOL   (United States)

^b HARVARD UNIVERSITY   (United States)

^c HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BENZYLOXYCARBONYLVALYLALANYLASPARTYL FLUOROMETHYL KETONE; CYCLOSPORIN A; F 16; PROTEIN TYROSINE PHOSPHATASE INHIBITOR; SMALL MOLECULE TRANSPORT AGENT; UNCLASSIFIED DRUG; 4 (2 (INDOL 3 YL)VINYL) 1 METHYLPYRIDINIUM; 4-(2-(INDOL-3-YL)VINYL)-1-METHYLPYRIDINIUM; CATION; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GROWTH INHIBITOR; INDOLE DERIVATIVE; PYRIDINIUM DERIVATIVE;

ARTICLE; BREAST EPITHELIUM; BREAST TUMOR; CANCER INHIBITION; CARCINOGENESIS; CELL ASSAY; CELL PROLIFERATION; GENE OVEREXPRESSION; HIGH THROUGHPUT SCREENING; HUMAN; HYPERPOLARIZATION; LIPOPHILICITY; MEMBRANE POTENTIAL; METABOLISM; MITOCHONDRION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; TUMOR CELL LINE; TUMOR GROWTH; ANIMAL; APOPTOSIS; BAGG ALBINO MOUSE; CELL CULTURE; CELL CYCLE; CELL DIVISION; CELL LINE; CELL MEMBRANE POTENTIAL; CHEMISTRY; DRUG EFFECT; EPITHELIUM CELL; EXPERIMENTAL NEOPLASM; GENETICS; MOUSE; PATHOLOGY; PROTO ONCOGENE; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE; ULTRASTRUCTURE;

ANIMALS; APOPTOSIS; BREAST NEOPLASMS; CATIONS; CELL CYCLE; CELL DIVISION; CELL LINE, TRANSFORMED; EPITHELIAL CELLS; GENES, ERBB-2; GROWTH INHIBITORS; HUMANS; INDOLES; MAMMARY NEOPLASMS, ANIMAL; MAMMARY NEOPLASMS, EXPERIMENTAL; MEMBRANE POTENTIALS; MICE; MICE, INBRED BALB C; MICE, TRANSGENIC; MITOCHONDRIA; PYRIDINIUM COMPOUNDS; RECEPTOR, ERBB-2; SIGNAL TRANSDUCTION; TUMOR CELLS, CULTURED;

EID: 0036654694     PISSN: 15356108     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1535-6108(02)00082-X     Document Type: Article

References (58)

1. Anderson, W.M., Patheja, H.S., Delinck, D.L., Baldwin, W.W., Smiley, S.T., and Chen, L.B. (1989). Inhibition of bovine heart mitochondrial and Paracoccus denitrificans NADH-ubiquinone reductase by dequalinium chloride and three structurally related quinolinium compounds. Biochem. Int. 19, 673-685.
2. Anderson, W.M., Delinck, D.L., Benninger, L., Wood, J.M., Smiley, S.T., and Chen, L.B. (1993). Cytotoxic effect of thiacarbocyanine dyes on human colon carcinoma cells and inhibition of bovine heart mitochondrial NADH-ubiquinone reductase activity via a rotenone-type mechanism by two of the dyes. Biochem. Pharmacol. 45, 691-696.
3. Bachelder, R.E., Wendt, M.A., Fujita, N., Tsuruo, T., and Mercurio, A.M. (2001). The cleavage of Akt/protein kinase B by death receptor signaling is an important event in detachment-induced apoptosis. J. Biol. Chem. 276, 34702-34707.
4. Bargmann, C.I., Hung, M.C., and Weinberg, R.A. (1986). The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature 319, 226-230.
5. Baselga, J. (2001). Phase I and II clinical trials of trastuzumab. Ann. Oncol. 12, S49-S55.
6. Bernal, S.D., Lampidis, T.J., Summerhayes, I.C., and Chen, L.B. (1982). Rhodamine-123 selectively reduces clonal growth of carcinoma cells in vitro. Science 218, 1117-1119.
7. Bernardi, P., Scorrano, L., Colonna, R., Petronilli, V., and Di Lisa, F. (1999). Mitochondria and cell death. Mechanistic aspects and methodological issues. Eur. J. Biochem. 264, 687-701.
8. Boitier, E., Rea, R., and Duchen, M.R. (1999). Mitochondria exert a negative feedback on the propagation of intracellular Ca2+ waves in rat cortical astrocytes. J. Cell Biol. 145, 795-808.
9. Britten, C.D., Rowinsky, E.K., Baker, S.D., Weiss, G.R., Smith, L., Stephenson, J., Rothenberg, M., Smetzer, L., Cramer, J., Collins, W., et al. (2000). A phase I and pharmacokinetic study of the mitochondrial-specific rhodacyanine dye analog MKT 077. Clin. Cancer Res. 6, 42-49.
10. Broekemeier, K.M., Dempsey, M.E., and Pfeiffer, D.R. (1989). Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria. J. Biol. Chem. 264, 7826-7830.
11. Cheng, E.H., Wei, M.C., Weiler, S., Flavell, R.A., Mak, T.W., Lindsten, T., and Korsmeyer, S.J. (2001). BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol. Cell 8, 705-711.
12. Chiba, Y., Kubota, T., Watanabe, M., Matsuzaki, S.W., Otani, Y., Teramoto, T., Matsumoto, Y., Koya, K., and Kitajima, M. (1998). MKT-077, localized lipophilic cation: antitumor activity against human tumor xenografts serially transplanted into nude mice. Anticancer Res. 18, 1047-1052.
13. Costantini, P., Petronilli, V., Colonna, R., and Bernardi, P. (1995). On the effects of paraquat on isolated mitochondria. Evidence that paraquat causes opening of the cyclosporin A-sensitive permeability transition pore synergistically with nitric oxide. Toxicology 99, 77-88.
14. Costantini, P., Jacotot, E., Decaudin, D., and Kroemer, G. (2000). Mitochondrion as a novel target of anticancer chemotherapy. J. Natl. Cancer Inst. 92, 1042-1053.
15. Dang, C.V., and Semenza, G.L. (1999). Oncogenic alterations of metabolism. Trends Biochem. Sci. 24, 68-72.
16. Green, D.R., and Reed, J.C. (1998). Mitochondria and apoptosis. Science 281, 1309-1312.
17. Gross, A., McDonnell, J.M., and Korsmeyer, S.J. (1999). BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13, 1899-1911.
18. Hiura, T.S., Li, N., Kaplan, R., Horwitz, M., Seagrave, J.C., and Nel, A.E. (2000). The role of a mitochondrial pathway in the induction of apoptosis by chemicals extracted from diesel exhaust particles. J. Immunol. 165, 2703-2711.
19. Hynes, N.E., and Stern, D.F. (1994). The biology of erbB-2/neu/HER-2 and its role in cancer. Biochim. Biophys. Acta 1198, 165-184.
20. Korsmeyer, S.J., McDonnell, T.J., Nunez, G., Hockenbery, D., and Young, R. (1990). Bcl-2: B cell life, death and neoplasia. Curr. Top. Microbiol. Immunol. 166, 203-207.
21. Koya, K., Li, Y., Wang, H., Ukai, T., Tatsuta, N., Kawakami, M., Shishido, T., and Chen, L.B. (1996). MKT-077, a novel rhodacyanine dye in clinical trials, exhibits anticarcinoma activity in preclinical studies based on selective mitochondrial accumulation. Cancer Res. 56, 538-543.
22. Kroemer, G., Dallaporta, B., and Resche-Rigon, M. (1998). The mitochondrial death/life regulator in apoptosis and necrosis. Annu. Rev. Physiol. 60, 619-642.
23. Lane, H.A., Beuvink, I., Motoyama, A.B., Daly, J.M., Neve, R.M., and Hynes, N.E. (2000). ErbB2 potentiates breast tumor proliferation through modulation of p27(Kip1)-Cdk2 complex formation: receptor overexpression does not determine growth dependency. Mol. Cell. Biol. 20, 3210-3223.
24. Liang, B.C., Miller, L., and Weller, A. (1999). Ethyl-nitrosourea transformed astrocytes exhibit mitochondrial membrane hyperpolarization and constrained apoptosis. Apoptosis 4, 89-97.
25. Liu, X., Kim, C.N., Yang, J., Jemmerson, R., and Wang, X. (1996). Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86, 147-157.
26. Lizard, G., Chignol, M.C., Chardonnet, Y., and Schmitt, D. (1994). Active cell membrane mechanisms involved in the exclusion of Rh 123 allow distinction between normal and tumoral cells. Cell Biol. Toxicol. 10, 399-406.
27. Moasser, M.M., Basso, A., Averbuch, S.D., and Rosen, N. (2001). The tyrosine kinase inhibitor ZD1839 ("Iressa") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res. 61, 7184-7188.
28. Modica-Napolitano, J.S., and Aprille, J.R. (1987). Basis for the selective cytotoxicity of rhodamine 123. Cancer Res. 47, 4361-4365.
29. Modica-Napolitano, J.S., and Aprille, J.R. (2001). Delocalized lipophilic cations selectively target the mitochondria of carcinoma cells. Adv. Drug Deliv. Rev. 49, 63-70.
30. Modica-Napolitano, J.S., Weiss, M.J., Chen, L.B., and Aprille, J.R. (1984). Rhodamine 123 inhibits bioenergetic function in isolated rat liver mitochondria. Biochem. Biophys. Res. Commun. 118, 717-723.
31. Modica-Napolitano, J.S., Koya, K., Weisberg, E., Brunelli, B.T., Li, Y., and Chen, L.B. (1996). Selective damage to carcinoma mitochondria by the rhodacyanine MKT-077. Cancer Res. 56, 544-550.
32. Muller, W.J., Sinn, E., Pattengale, P.K., Wallace, R., and Leder, P. (1988). Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 54, 105-115.
33. Nadakavukaren, K.K., Nadakavukaren, J.J., and Chen, L.B. (1985). Increased rhodamine 123 uptake by carcinoma cells. Cancer Res. 45, 6093-6099.
34. Neve, R.M., Lane, H.A., and Hynes, N.E. (2001). The role of overexpressed HER2 in transformation. Ann. Oncol. 12, S9-S13.
35. Noonberg, S.B., and Benz, C.C. (2000). Tyrosine kinase inhibitors targeted to the epidermal growth factor receptor subfamily: role as anticancer agents. Drugs 59, 753-767.
36. Ohnami, S., Matsumoto, N., Nakano, M., Aoki, K., Nagasaki, K., Sugimura, T., Terada, M., and Yoshida, T. (1999). Identification of genes showing differential expression in antisense K-ras-transduced pancreatic cancer cells with suppressed tumorigenicity. Cancer Res. 59, 5565-5571.
37. Olayioye, M.A., Neve, R.M., Lane, H.A., and Hynes, N.E. (2000). The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J. 19, 3159-3167.
38. Propper, D.J., Braybrooke, J.P., Taylor, D.J., Lodi, R., Styles, P., Cramer, J.A., Collins, W.C., Levitt, N.C., Talbot, D.C., Ganesan, T.S., and Harris, A.L. (1999). Phase I trial of the selective mitochondrial toxin MKT077 in chemoresistant solid tumours. Ann. Oncol. 10, 923-927.
39. Raha, S., and Robinson, B.H. (2001). Mitochondria, oxygen free radicals, and apoptosis. Am. J. Med. Genet. 106, 62-70.
40. Reichmann, E., Schwarz, H., Deiner, E.M., Leitner, I., Eilers, M., Berger, J., Busslinger, M., and Beug, H. (1992). Activation of an inducible c-FosER fusion protein causes loss of epithelial polarity and triggers epithelial-fibroblastoid cell conversion. Cell 71, 1103-1116.
41. Roh, H., Pippin, J., and Drebin, J.A. (2000). Down-regulation of HER2/neu expression induces apoptosis in human cancer cells that overexpress HER2/neu. Cancer Res. 60, 560-565.
42. Rubin, I., and Yarden, Y. (2001). The basic biology of HER2. Ann. Oncol. 12, S3-S8.
43. Scaduto, R.C., Jr., and Grotyohann, L.W. (1999). Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives. Biophys. J. 76, 469-477.
44. Scorrano, L., Petronilli, V., and Bernardi, P. (1997). On the voltage dependence of the mitochondrial permeability transition pore. A critical appraisal. J. Biol. Chem. 272, 12295-12299.
45. Scorrano, L., Petronilli, V., Colonna, R., Di Lisa, F., and Bernardi, P. (1999). Chloromethyltetramethylrosamine (Mitotracker Orange) induces the mitochondrial permeability transition and inhibits respiratory complex I. Implications for the mechanism of cytochrome c release. J. Biol. Chem. 274, 24657-24663.
46. Seymour, L.K. (2001). Epidermal growth factor receptor as a target: recent developments in the search for effective new anti-cancer agents. Curr. Drug Targets 2, 117-133.
47. Somasundaram, K. (2000). Tumor suppressor p53: regulation and function. Front. Biosci. 5, D424-D437.
48. Stockwell, B.R., Haggarty, S.J., and Schreiber, S.L. (1999). High-throughput screening of small molecules in miniaturized mammalian cell-based assays involving post-translational modifications. Chem. Biol. 6, 71-83.
49. Summerhayes, I.C., Lampidis, T.J., Bernal, S.D., Nadakavukaren, J.J., Nadakavukaren, K.K., Shepherd, E.L., and Chen, L.B. (1982). Unusual retention of rhodamine 123 by mitochondria in muscle and carcinoma cells. Proc. Natl. Acad. Sci. USA 79, 5292-5296.
50. Sun, X., Wong, J.R., Song, K., Hu, J., Garlid, K.D., and Chen, L.B. (1994). AA1, a newly synthesized monovalent lipophilic cation, expresses potent in vivo antitumor activity. Cancer Res. 54, 1465-1471.
51. Tikhomirov, O., and Carpenter, G. (2001). Caspase-dependent cleavage of ErbB-2 by geldanamycin and staurosporin. J. Biol. Chem. 276, 33675-33680.
52. Vanden Hoek, T.L., Becker, L.B., Shao, Z., Li, C., and Schumacker, P.T. (1998). Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes. J. Biol. Chem. 273, 18092-18098.
53. Warburg, O. (1956). On the origin of cancer cells. Science 123, 309-314.
54. Wei, M.C., Zong, W.X., Cheng, E.H., Lindsten, T., Panoutsakopoulou, V., Ross, A.J., Roth, K.A., MacGregor, G.R., Thompson, C.B., and Korsmeyer, S.J. (2001). Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292, 727-730.
55. Winer, E.P., and Burstein, H.J. (2001). New combinations with herceptin((r)) in metastatic breast cancer. Oncology 61 (Suppl.), 50-57.
56. Yarden, Y. (2001). Biology of HER2 and its importance in breast cancer. Oncology 61 (Suppl.), 1-13.
57. Zarbl, H., Latreille, J., and Jolicoeur, P. (1987). Revertants of v-fos-transformed fibroblasts have mutations in cellular genes essential for transformation by other oncogenes. Cell 51, 357-369.
58. Zwick, E., Bange, J., and Ullrich, A. (2001). Receptor tyrosine kinase signalling as a target for cancer intervention strategies. Endocr. Relat. Cancer 8, 161-173.