GTI-2040, an antisense agent targeting the small subunit component (R2) of human ribonucleotide reductase, shows potent antitumor activity against a variety of tumors

Cancer Research

Volumn 63, Issue 11, 2003, Pages 2802-2811

  Lee, Yoon ^a   Vassilakos, Aikaterini ^a   Feng, Ningping ^a   Lam, Viengthong ^a   Xie, Hongsheng ^a   Wang, Ming ^a   Jin, Hongnan ^a   Xiong, Keyong ^a   Liu, Chenyi ^a   Wright, Jim ^a   Young, Aiping ^a  

^a Lorus Therapeutics Inc   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; ANTISENSE OLIGODEOXYNUCLEOTIDE; DOXORUBICIN; FLUDARABINE; FLUDARABINE PHOSPHATE; FLUOROURACIL; GEMCITABINE; GTI 2040; HYDROXYUREA; MESSENGER RNA; RIBONUCLEOTIDE REDUCTASE; UNCLASSIFIED DRUG; VINBLASTINE;

ADENOCARCINOMA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; ASTROCYTOMA; BREAST TUMOR; COLON TUMOR; CONTROLLED STUDY; DRUG SELECTIVITY; DRUG TARGETING; ENZYME SUBUNIT; FEMALE; GLIOBLASTOMA; HUMAN; HUMAN CELL; KIDNEY TUMOR; LIVER TUMOR; LUNG TUMOR; MELANOMA; METASTASIS; MOUSE; NONHUMAN; OVARY TUMOR; PANCREAS TUMOR; PRIORITY JOURNAL; PROSTATE TUMOR; TUMOR; TUMOR CELL CULTURE; UTERINE CERVIX TUMOR;

ANIMALS; BURKITT LYMPHOMA; CPG ISLANDS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOWN-REGULATION; FEMALE; FIBROSARCOMA; HUMANS; LUNG NEOPLASMS; MELANOMA; MICE; MICE, INBRED BALB C; MICE, NUDE; MICE, SCID; NEOPLASMS; OLIGONUCLEOTIDES, ANTISENSE; RIBONUCLEOTIDE REDUCTASES; RNA, MESSENGER; TUMOR CELLS, CULTURED; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 0038615898     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (54)

1. Cory, J. G. Purine and pyrimidine nucleotide metabolism. In: T. Devlin (ed.) Biochemistry with Clinical Correlations, 4th ed., pp. 489-523. New York: Wiley-Liss, 1997.
2. Tonin, P. N., Stallings, R. L., Carman, M. D., Bertino, J. R., Wright, J. A., Srinivasan, P. R., and Lewis, W. H. Chromosomal assignment of amplified genes in hydroxyurea-resistant hamster cells. Cytogenet. Cell Genet., 45: 102-108, 1987.
3. Engstrom, Y., Eriksson, S., Jildevik, I., Skog, S., Thelander, L., and Tribukait, B. Cell cycle-dependent expression of mammalian ribonucleotide reductase. J. Biol. Chem., 260: 9114-9116, 1985.
4. Nocentini, G. Ribonucleotide reductase inhibitors: new strategies for cancer chemotherapy. Crit. Rev. Oncol. Hematol., 22: 89-126, 1996.
5. Chabes, A., and Thelander, L. Controlled protein degradation regulates ribonucleotide reductase activity in proliferating mammalian cells during the normal cell cycle and in response to DNA damage and replication blocks. J. Biol. Chem., 275: 17747-17753, 2000.
6. Albert, D. A., and Rozengurt, E. Synergistic and coordinate expression of the genes encoding ribonucleotide reductase subunits in Swiss 3T3 cells: effect of multiple signal-transduction pathways. Proc. Natl. Acad. Sci. USA, 89: 1597-1601, 1992.
7. Albert, D. A., and Nodzenski, E. Ribonucleotide reductase gene expression during cyclic AMP-induced cell cycle arrest in T lymphocytes. Exp. Cell Res., 203: 476-482, 1992.
8. Albert, D. A., and Rozengurt, E. Opposite effects of cyclic AMP on the expression of the genes encoding ribonucleotide reductase in Swiss 3T3 and RAT 1 cells. Biochem. Biophys. Res. Commun., 196: 642-649, 1993.
9. Fredriksson, J. M., and Nedergaard, J. Norepinephrine specifically stimulates ribonucleotide reductase subunit R2 gene expression in proliferating brown adipocytes: mediation via a cAMP/PKA pathway involving Src and Erk1/2 kinases. Exp. Cell Res., 274: 207-215, 2002.
10. Tanaka, H., Arakawa, H., Yamaguchi, T., Shiraishi, K., Fukuda, S., Matsui, K., Takei, Y., and Nakamura, Y. A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature (Lond.), 404: 42-49, 2000.
11. Nakano, K., Balint, E., Ashcroft, M., and Vousden, K. H. A ribonucleotide reductase gene is a transcriptional target of p53 and p73. Oncogene, 19: 4283-4289, 2000.
12. Yamaguchi, T., Matsuda, K., Sagiya, Y., Iwadate, M., Fujino, M. A., Nakamura, Y., and Arakawa, H. p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint. Cancer Res., 61: 8256-8262, 2001.
13. Guittet, O., Hakansson, P., Voevodskaya, N., Fridd, S., Graslund, A., Arakawa, H., Nakamura, Y., and Thelander, L, Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with the R1 protein, which is expressed both in resting cells in response to DNA damage and in proliferating cells. J. Biol. Chem., 276: 40647-40651, 2001.
14. Crenshaw, T. R., and Cory, J. G. Overexpression of protein disulfide isomerase-like protein in a mouse leukemia L1210 cell line selected for resistance to 4-methyl-5- amino-1-formylisoquinoline thiosemicarbazone, a ribonucleotide reductase inhibitor. Adv. Enzyme Regul., 42: 143-157, 2002.
15. Green, D. A., Antholine, W. E., Wong, S. J., Richardson, D. R., and Chitambar, C. R. Inhibition of malignant cell growth by 311, a novel iron chelator of the pyridoxal isonicotinoyl hydrazone class: effect on the R2 subunit of ribonucleotide reductase. Clin. Cancer Res., 7: 3574-3579, 2001.
16. Gao, Y., Liehr, S., and Cooperman, B. S. Affinity-driven selection of tripeptide inhibitors of ribonucleotide reductase. Bioorg. Med. Chem. Lett., 12: 513-515, 2002.
17. Fagny, C., Vandevelde, M., Svoboda, M., and Robberecht, P. Ribonucleotide reductase and thymidine phosphorylation: two potential targets of azodicarbonamide. Biochem. Pharmacol., 64: 451-456, 2002.
18. Feun, L., Modiano, M., Lee, K., Mao, J., Marini, A., Savaraj, N., Plezia, P., Almassian, B., Colacino, E., Fischer, J., and MacDonald, S. Phase I and pharmacokinetic study of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) using a single intravenous dose schedule. Cancer Chemother. Pharmacol., 50: 223-229, 2002.
19. Angus, S. P., Wheeler, L. J., Ranmal, S. A., Zhang, X., Markey, M. P., Mathews, C. K., and Knudsen, E. S. The retinoblastoma tumor suppressor targets dNTP metabolism to regulate DNA replication, J. Biol. Chem., 277: 44376-44384, 2002.
20. Fan, H., Villegas, C., Huang, A., and Wright, J. A. The mammalian ribonucleotide reductase R2 component cooperates with a variety of oncogenes in mechanisms of cellular transformation. Cancer Res., 58: 1650-1653, 1998.
21. Fan, H., Villegas, C., and Wright, J. A. Ribonucleotide reductase R2 component is a novel malignancy determinant that cooperates with activated oncogenes to determine transformation and malignant potential. Proc. Natl. Acad. Sci. USA, 93: 14036-14040, 1996.
22. Huang, A., Fan, H., Taylor, W. R., and Wright, J. A. Ribonucleotide reductase R2 gene expression and changes in drug sensitivity and genome stability. Cancer Res., 57: 4876-4881, 1997.
23. Goan, Y. G., Zhou, B., Hu, E., Mi, S., and Yen, Y. Overexpression of ribonucleotide reductase as a mechanism of resistance to 2,2-defluorodeoxycyctidine in the human KB cancer cell line. Cancer Res., 59: 4204-4207, 1999.
24. Zhou, B. S., Hsu, N. Y., Pan, B. C., Doroshow, J. H., and Yen, Y. Overexpression of ribonucleotide reductase in transfected human KB cells increases their resistance to hydroxyurea: M2 but not M1 is sufficient to increase resistance to hydroxyurea in transfected cells. Cancer Res., 55: 1328-1333, 1995.
25. Chen, S., Zhou, B., He, F., and Yen, Y. Inhibition of human cancer cell growth by inducible expression of human ribonucleotide reductase antisense cDNA. Antisense Nucleic Acid Drug Dev., 10: 111-116, 2000.
26. Kuschak, T. I., Kuschak, B. C., Taylor, C. L., Wright, J. A., Wiener, F., and Mai, S. c-Myc initiates illegitimate replication of the ribonucleotide reductase R2 gene. Oncogene, 21: 909-920, 2002.
27. Opalinska, J. B., and Gewirtz, A. M. Nucleic-acid therapeutics: basic principles and recent applications. Nat. Rev. Drug Discov., 1: 503-514, 2002.
28. Braasch, D. A., and Corey, D. R. Novel antisense and peptide nucleic acid strategies for controlling gene expression. Biochemistry. 41: 4504-4510, 2002.
29. Flaherty, K. T., Stevenson, J. P., and O'Dwyer, P. J. Antisense therapeutics: lessons from early clinical trials. Curr. Opin. Oncol., 13: 499-505, 2001.
30. Field, A. K., and Goodchild, J. Antisense oligonucleotides: rational drug design for genetic pharmacology. Exp. Opin. Investig. Drugs, 4: 799-821, 1995.
31. Dolnick, B. J. Antisense agents in cancer research and therapeutics. Cancer Invest., 9: 185-194, 1991.
32. Welch, D. R., Bisi, J. E., Miller, B. E., Conaway, D., Seftor, E. A., Yohem, K. H., Gilmore, L. B., Seftor, R. E., Nakajima, M., and Hendrix, M. J. Characterization of a highly invasive and spontaneously metastatic human malignant melanoma cell line. Int. J. Cancer, 47: 227-237, 1991.
33. Choy, B. K., McClarty, G. A., Chan, A. K., Thelander, L., and Wright, J. A. Molecular mechanis of drug resistance involving ribonucleotide reductase: hydroxyurea resistance in a series of clonally related mouse cell lines selected in the presence of increasing drug concentrations. Cancer Res., 48: 2029-2035, 1988.
34. Mann, G. J., Graslund, A., Ochiai, E., Ingemarson, R., and Thelander, L. Purification and characterization of recombinant mouse and herpes simplex virus ribonucleotide reductase R2 subunit. Biochemistry, 30: 1939-1947, 1991.
35. Chan, A. K., Litchfield, D. W., and Wright, J. A. Phosphorylation of ribonucleotide reductase R2 protein: in vivo and in vitro evidence of a role of p34cdc2 CDK2 protein kinases. Biochemistry, 32: 12835-12840, 1993.
36. Bhatia, P., Taylor, W. R., Greenberg, A. H., and Wright, J. A. Comparison of glyceraldehyde-3-phosphate dehydrogenase and 28S-ribosomal RNA gene expression as RNA loading controls for Northern blot analysis of cell lines of varying malignant potential. Anal. Biochem., 216: 223-226, 1994.
37. McClarty, G. A., Chan, A. K., Engstrom, Y., Wright, J. A., and Thelander, L. Elevated expression of M1 and M2 components and drug-induced posttranslational modulation of ribonucleotide reductase in a hydroxyurea-resistant mouse cell line. Biochemistry, 26: 8004-8011, 1987.
38. Wright, J. A., Alam, T. G., McClarty, G. A., Tagger, A. Y., and Thelander, L. Altered expression of ribonucleotide reductase and role of M2 gene amplification in hydroxyurea-resistant hamster, mouse, rat, and human cell lines. Somatic Cell Mol. Genet., 13: 155-165, 1987.
39. Thelander, L., and Berg, P. Isolation and characterization of expressible cDNA clones encoding the M1 and M2 subunits of mouse ribonucleotide reductase. Mol. Cell. Biol., 6: 3433-3442, 1986.
40. Pavloff, N., Rivard, D., Masson, S., Shen, S., and Mes-Masson, A. Sequence analysis of the large and small subunits of human ribonucleotide reductase. DNA Seq., 2: 227-234, 1992.
41. Takeda, E., and Weber, G. Role of ribonucleotide reductase in expression of the neoplastic program. Life Sci., 28: 1007-1014, 1981.
42. Jensen, R. A., Page, D. L., and Holt, J. T. Identification of genes expressed in premalignant breast disease by microscopy-directed cloning. Proc. Natl. Acad. Sci. USA, 91: 9257-9261, 1994.
43. Saeki, T., Takashima, S., Ohsumi, S., Saeki, H., Takiyama, W., Kurita, A., and Yokoyama, N. Ribonucleotide reductase highly expressed in breast cancer patients with hormone receptors. Proc. Am. Soc. Clin. Oncol., 1997.
44. Monteith, D. K., Henry, S. P., Howard, R. B., Flournoy, S., Levin, A. A., Bennett, F., and Crooke, S. T. Immune stimulation: a class effect of phosphorothioate oligode-oxynucleotides in rodents. Anti-Cancer Drug Design, 12: 421-432, 1997.
45. Frenkel, G. D., and Caffrey, P. B. A prevention strategy for circumventing drug resistance in cancer chemotherapy. Curr. Pharm. Des., 7: 1595-1614, 2001.
46. Krieg, A. M. Immune effects and mechanisms of action of CpG motifs. Vaccine, 19: 618-622, 2001.
47. Krieg, A. M. CpG motifs in bacterial DNA and their immune effects. Annu. Rev. Immunol., 20: 709-760, 2002.
48. Agrawal, S., and Akhtar, S. Advances in antisense efficacy and delivery. Trends Biotechnol., 13: 197-199, 1995.
49. Akhtar, S., Hughes, M. D., Khan, A., Bibby, M., Hussain, M., Nawaz, Q., Double, J., and Sayyed, P. The delivery of antisense therapeutics. Adv. Drug Deliv. Rev., 44: 3-21, 2000.
50. Dokka, S., and Rojanasakul, Y. Novel non-endocytic delivery of antisense oligonucleotides. Adv. Drug Deliv. Rev., 44: 35-49, 2000.
51. Crooke, S. T. Proof of mechanism of antisense drugs. Antisense Nucleic Acid Drug Dev., 6: 145-147, 1996.
52. Whitmore, M. M., Li, S., Falo, L., Jr., and Huang, L. Systemic administration of LPD prepared with CpG oligonucleotides inhibits the growth of established pulmonary metastases by stimulating innate and acquired antitumor immune response. Cancer Immunol. Immunother., 50: 503-514, 2001.
53. Miraglia, L., Watt, A. T., Graham, M. J., and Crooke, S. T. Variations in mRNA content have no effect on the potency of antisense oligonucleotide. Antisense Nucleic Acid Drug Dev., 10: 453-461, 2000.
54. Hayflick, L. Mortality and immortality at the cellular level: a review. Biochemistry, 62: 1180-1190, 1997.