ODN 491, a novel antisense oligodeoxynucleotide that targets thymidylate synthase, exerts cell-specific effects in human tumor cell lines

DNA and Cell Biology

Volumn 27, Issue 5, 2008, Pages 229-240

  Jason, Tracey L H ^a,b   Figueredo, Rene ^a,c   Ferguson, Peter J ^a,c   Vincent, Mark D ^a,b,c   Berg, Randal W ^a,b,c   Koropatnick, James ^a,b,c  

^a LONDON REGIONAL CANCER PROGRAM   (Canada)

^b WESTERN UNIVERSITY   (Canada)

^c LONDON HEALTH SCIENCES CENTRE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGODEOXYNUCLEOTIDE; CISPLATIN; FLOXURIDINE; MESSENGER RNA; OLIGODEOXYNUCLEOTIDE 491; RALTITREXED; THYMIDYLATE SYNTHASE;

APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CELL PROLIFERATION; CELL STRAIN MCF 7; CONTROLLED STUDY; CORRELATION ANALYSIS; CULTURE MEDIUM; DNA REPLICATION; DRUG CYTOTOXICITY; DRUG EFFECT; DRUG EFFICACY; DRUG RESPONSE; DRUG SENSITIVITY; DRUG TARGETING; HELA CELL; HUMAN; HUMAN CELL; NEOPLASM; PRIORITY JOURNAL;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL PROLIFERATION; FLOW CYTOMETRY; HELA CELLS; HUMANS; OLIGONUCLEOTIDES, ANTISENSE; RNA, MESSENGER; THYMIDYLATE SYNTHASE; TRANSCRIPTION, GENETIC; TRANSFECTION;

EID: 43249101997     PISSN: 10445498     EISSN: None     Source Type: Journal    
DOI: 10.1089/dna.2007.0674     Document Type: Article

References (62)

1. Banerjee, D. (1999). Technology evaluation: G-3139. Curr Opin Mol Ther 1, 404-408.
2. Benimetskaya, L., Lai, J.C., Khvorova, A., Wu, S., Hua, E., Miller, P., Zhang, L.M., and Stein, C.A. (2004). Relative Bcl-2 independence of drug-induced cytotoxicity and resistance in 518A2 melanoma cells. Clin Cancer Res 10, 8371-8379.
3. Berg, R.W., Ferguson, P.J., DeMoor, J.M., Vincent, M.D., and Koropatnick, D.J. (2002). The means to an end of tumor cell resistance to chemotherapeutic drugs targeting thymidylate synthase: shoot the messenger. Curr Drug Targets 3, 297-309.
4. Berg, R.W., Ferguson, P.J., Vincent, M.D., and Koropatnick, D.J. (2003). A "combination oligonucleotide" antisense strategy to downregulate thymidylate synthase and decrease tumor cell growth and drug resistance. Cancer Gene Ther 10, 278-286.
5. 2/M cell cycle arrest induced by antisense oligodeoxynucleotide targeting thymidylate synthase. J Pharmacol Exp Ther 298, 477-484.
6. Chu, E., Callender, M.A., Farrell, M.P., and Schmitz, J.C. (2003). Thymidylate synthase inhibitors as anticancer agents: from bench to bedside. Cancer Chemother Pharmacol 52 (Suppl 1), S80-S89.
7. Crooke, S.T. (2004). Progress in antisense technology. Annu Rev Med 55, 61-95.
8. Danenberg, P.V. (1977). Thymidylate synthetase - a target enzyme in cancer chemotherapy. Biochim Biophys Acta 473, 73-92.
9. Danenberg, P.V., Malli, H., and Swenson, S. (1999). Thymidylate synthase inhibitors. Semin Oncol 26, 621-631.
10. DeMoor, J.M., Vincent, M.D., Collins, O.M., and Koropatnick, J. (1998). Antisense nucleic acids targeted to the thymidylate synthase (TS) mRNA translation start site stimulate TS gene transcription. Exp Cell Res 243, 11-21.
11. Dias, N., and Stein, C.A. (2002). Potential roles of antisense oligonucleotides in cancer therapy. The example of Bcl-2 antisense oligonucleotides. Eur J Pharm Biopharm 54, 263-269.
12. Edler, D., Hallstrom, M., Johnston, P.G., Magnusson, I., Ragnhammar, P., and Blomgren, H. (2000). Thymidylate synthase expression: an independent prognostic factor for local recurrence, distant metastasis, disease-free and overall survival in rectal cancer. Clin Cancer Res 6, 1378-1384.
13. Ferguson, P.J., Collins, O., Dean, N.M., DeMoor, J., Li, C.S., Vincent, M.D., and Koropatnick, J. (1999). Antisense downregulation of thymidylate synthase to suppress growth and enhance cytotoxicity of 5-FUdR, 5-FU and Tomudex in HeLa cells. Br J Pharmacol 127, 1777-1786.
14. Ferguson, P.J., DeMoor, J.M., Vincent, M.D., and Koropatnick, J. (2001). Antisense-induced down-regulation of thymidylate synthase and enhanced cytotoxicity of 5-FUdR in 5-FUdR-resistant HeLa cells. Br J Pharmacol 134, 1437-1446.
15. Flynn, J., Berg, R.W., Wong, T., Van Aken, M., Vincent, M.D., Fukushima, M., and Koropatnick, J. (2006). Therapeutic potential of antisense oligo deoxynucleotides to down-regulate thymidylate synthase in mesothelioma. Mol Cancer Thet 5, 1423-1433.
16. Geiger, T., Muller, M., Monia, B.P., and Fabbro, D. (1997). Antitumor activity of a C-raf antisense oligonucleotide in combination with standard chemotherapeutic agents against various human tumors transplanted subcutaneously into nude mice. Clin Cancer Res 3, 1179-1185.
17. Gleave, M., and Chi, K.N. (2005). Knock-down of the cytoprotective gene, clusterin, to enhance hormone and chemosensitivity in prostate and other cancers. Ann N Y Acad Sci 1058, 1-15.
18. Gleave, M.E., and Monia, B.P. (2005). Antisense therapy for cancer. Nat Rev Cancer 5, 468-479.
19. Gorlick, R., and Bertino, J.R. (1999). Drug resistance in colon cancer. Semin Oncol 26, 606-611.
20. Higashiyama, M., Kodama, K., Yokouchi, H., Takami, K., Fukushima, M., Minamigawa, K., Takano, T., and Kobayashi, H. (2001). Thymidylate synthase and dihydropyrimidine dehydrogenase activities in non-small cell lung cancer tissues: relationship with in vitro sensitivity to 5-fluorouracil. Lung Cancer 34, 407-416.
21. Holmlund, J.T. (2003). Applying antisense technology: Affinitak and other antisense oligonucleotides in clinical development. Ann N Y Acad Sci 1002, 244-251.
22. Jason, T.L.H., Berg, R.W., Vincent, M.D., and Koropatnick, J. (2007). Antisense targeting of thymidylate synthase (TS) mRNA increases TS gene transcription and TS protein: effects on human tumor cell sensitivity to TS enzyme inhibiting drugs. Gene Expr 13, 227-239.
23. Jason, T.L.H., Koropatnick, D.J., and Berg, R.W. (2004). Toxicology of antisense therapeutics. Toxicol Appl Pharmacol 201, 66-83.
24. Johnson, L.F. (1994). Posttranscriptional regulation of thymidylate synthase gene expression. J Cell Biochem 54, 387-392.
25. Ju, J., Pedersen-Lane, J., Maley, F., and Chu, E. (1999). Regulation of p53 expression by thymidylate synthase. Proc Natl Acad Sci USA 96, 3769-3774.
26. Keyomarsi, K., and Moran, R.G. (1988). Mechanism of the cytotoxic synergism of fluoropyrimidines and folinic acid in mouse leukemic cells. J Biol Chem 263, 14402-14409.
27. Krieg, A.M. (1999). Mechanisms and applications of immune stimulatory CpG oligodeoxynucleotides. Biochim Biophys Acta 1489, 107-116.
28. Kurreck, J. (2003). Antisense technologies. Improvement through novel chemical modifications. Eur J Biochem 270, 1628-1644.
29. Lai, J.C., Benimetskaya, L., Khvorova, A., Wu, S., Hua, E., Miller, P., and Stein, C.A. (2005). Phosphorothioate oligodeoxynucleotides and G3139 induce apoptosis in 518A2 melanoma cells. Mol Cancer Ther 4, 305-315.
30. Lai, J.C., Tan, W., Benimetskaya, L., Miller, P., Colombini, M., and Stein, C.A. (2006). A pharmacologic target of G3139 in melanoma cells may be the mitochondrial VDAC. Proc Natl Acad Sci USA 103, 7494-7499.
31. Lee, Y., Vassilakos, A., Feng, N., Avolio, T., Jin, H., Viau, S., Wang, M., Courssaris, B., Xiong, K., Wright, J., and Young, A. (2006a). Anti-proliferative and anti-tumor effects of antisense oligonucleotide GTI-2601 targeted against human thioredoxin. Anticancer Drugs 17, 143-154.
32. Lee, Y., Vassilakos, A., Feng, N., Jin, H., Wang, M., Xiong, K., Wright, J., and Young, A. (2006b). GTI-2501, an antisense agent targeting R1, the large subunit of human ribonucleotide reductase, shows potent anti-tumor activity against a variety of tumors. Int J Oncol 28, 469-478.
33. Lee, Y., Vassilakos, A., Feng, N., Lam, V., Xie, H., Wang, M., Jin, H., Xiong, K., Liu, C., Wright, J., and Young, A. (2003). 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 Res 63, 2802-2811.
34. Lehman, N.L. (2002). Future potential of thymidylate synthase inhibitors in cancer therapy. Expert Opin Investig Drugs 11, 1775-1787.
35. Lin, S.B., Ts'O, P.O., Sun, S.K., Choo, K.B., Yang, F.Y., Lim, Y.P., Tsai, H.L., and Au, L.C. (2001). Inhibition of thymidylate synthase activity by antisense oligodeoxynucleotide and possible role in thymineless treatment. Mol Pharmacol 60, 474-479.
36. Liu, J., Schmitz, J.C., Lin, X., Tai, N., Yan, W., Farrell, M., Bailly, M., Chen, T., and Chu, E. (2002). Thymidylate synthase as a translational regulator of cellular gene expression. Biochim Biophys Acta 1587, 174-182.
37. Longley, D.B., Harkin, D.P., and Johnston, P.G. (2003). 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3, 330-338.
38. Lopes, D., and Mayer, L.D. (2002). Pharmacokinetics of Bcl-2 antisense oligonucleotides (G3139) combined with doxorubicin in SCID mice bearing human breast cancer solid tumor xenografts. Cancer Chemother Pharmacol 49, 57-68.
39. Lou, T.F., Gray, C.W., and Gray, D.M. (2003). The reduction of Raf-1 protein by phosphorothioate ODNs and siRNAs targeted to the same two mRNA sequences. Oligonucleotides 13, 313-324.
40. Ma, T., Zhu, Z.G., Ji, Y.B., Zhang, Y., Yu, Y.Y., Liu, B.Y., Yin, H.R., and Lin, Y.Z. (2004). Correlation of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase with sensitivity of gastrointestinal cancer cells to 5-fluorouracil and 5-fluoro-2′- deoxyuridine. World J Gastroenterol 10, 172-176.
41. Mercatante, D.R., Mohler, J.L., and Kole, R. (2002). Cellular response to an antisense-mediated shift of Bcl-x pre-mRNA splicing and antineoplastic agents. J Biol Chem 277, 49374-49382.
42. Mirjolet, J.F., Barberi-Heyob, M., Merlin, J.L., Marchal, S., Etienne, M.C., and Bey, P. (1998). Thymidylate synthase expression and activity: relation to S-phase parameters and 5-fluorouracil sensitivity. Br J Cancer 78, 62-68.
43. Miyake, H., Hara, J., Kamidono, S., and Gleave, M.E. (2001). Synergistic chemosensitization and inhibition of tumor growth and metastasis by the antisense oligodeoxynucleotides targeting clusterin gene in a human bladder cancer model. Clin Cancer Res 7, 4245-4252.
44. Nielsen, O.H., Vainer, B., and Rask-Madsen, J. (2001). Review article: the treatment of inflammatory bowel disease with 6-mercaptopurine or azathioprine. Aliment Pharmacol Ther 15, 1699-1708.
45. Novina, C.D., and Sharp, P.A. (2004). The RNAi revolution. Nature 430, 161-164.
46. Orr, R.M. (2001). GTI-2040. Lorus Therapeutics. Curr Opin Investig Drugs 2, 1462-1466.
47. Paranjape, J.M., Xu, D., Kushner, D.M., Okicki, J., Lindner, D.J., Cramer, H., Silverman, R.H., and Leaman, D.W. (2006). Human telomerase RNA degradation by 2′-5′-linked oligoadenylate antisense chimeras in a cell-free system, cultured tumor cells, and murine xenograft models. Oligonucleotides 16, 225-238.
48. Park, Y., Chang, Y.S., Lee, S.W., Cho, S.Y., Kim, Y.K., Min, K.U., Kim, Y.Y., Cho, S.H., and Sung, Y.C. (2001). The enhanced effect of a hexameric deoxyriboguanosine run conjugation to CpG oligodeoxynucleotides on protection against allergic asthma. J Allergy Clin Immunol 108, 570-576.
49. Peters, G.J., Backus, H.H., Freemantle, S., van Triest, B., Codacci-Pisanelli, G., van der Wilt, C.L., Smid, K., Lunec, J., Calvert, A.H., Marsh, S., McLeod, H.L., Bloemena, E., Meijer, S., Jansen, G., van Groeningen, C.J., and Pinedo, H.M. (2002). Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism. Biochim Biophys Acta 1587, 194-205.
50. Raffo, A., Lai, J.C., Stein, C.A., Miller, P., Scaringe, S., Khvorova, A., and Benimetskaya, L. (2004). Antisense RNA down-regulation of bcl-2 expression in DU145 prostate cancer cells does not diminish the cytostatic effects of G3139 (Oblimersen). Clin Cancer Res 10, 3195-3206.
51. Rahman, L., Voeller, D., Rahman, M., Lipkowitz, S., Allegra, C., Barrett, J.C., Kaye, F.J., and Zajac-Kaye, M. (2004). Thymidylate synthase as an oncogene: a novel role for an essential DNA synthesis enzyme. Cancer Cell 5, 341-351.
52. Rose, M.G., Farrell, M.P., and Schmitz, J.C. (2002). Thymidylate synthase: a critical target for cancer chemotherapy. Clin Colorectal Cancer 1, 220-229.
53. Rustum, Y.M. (2004). Thymidylate synthase: a critical target in cancer therapy? Front Biosci 9, 2467-2473.
54. Saga, Y., Suzuki, M., Mizukami, H., Kohno, T., Takei, Y., Fukushima, M., and Ozawa, K. (2003). Overexpression of thymidylate synthase mediates desensitization for 5-fluorouracil of tumor cells. Int J Cancer 106, 324-326.
55. Sander, J.W., and Mitchell, T.N. (2001). Levetiracetam: a new antiepileptic drug for the adjunctive therapy of chronic epilepsy. Drugs Today 37, 665-673.
56. Schmitz, J.C., Chen, T.M., and Chu, E. (2004). Small interfering double-stranded RNAs as therapeutic molecules to restore chemosensitivity to thymidylate synthase inhibitor compounds. Cancer Res 64, 1431-1435.
57. Tolcher, A.W. (2001). Preliminary phase I results of G3139 (bcl-2 antisense oligonucleotide) therapy in combination with docetaxel in hormone refractory prostate cancer. Semin Oncol 28, 67-70.
58. Tu, G.C., and Tu, X. (2001). GTI-2501. Lorus Therapeutics. Curr Opin Investig Drugs 2, 1467-1470.
59. van Triest, B., Pinedo, H.M., van Hensbergen, Y., Smid, K., Telleman, F., Schoenmakers, P.S., van der Wilt, C.L., van Laar, J.A., Noordhuis, P., Jansen, G., and Peters, G.J. (1999). Thymidylate synthase level as the main predictive parameter for sensitivity to 5-fluorouracil, but not for folate-based thymidylate synthase inhibitors, in 13 nonselected colon cancer cell lines. Clin Cancer Res 5, 643-654.
60. Wall, N.R., and Shi, Y. (2003). Small RNA: can RNA interference be exploited for therapy? Lancet 362, 1401-1403.
61. Wasan, E.K., Waterhouse, D., Sivak, O., Bally, M.B., Klasa, R.J., and Wasan, K.M. (2002). Plasma protein binding, lipoprotein distribution and uptake of free and lipid-associated BCL-2 antisense oligodeoxynucleotides (G3139) in human melanoma cells. Int J Pharm 241, 57-64.
62. Zamaratski, E., Pradeepkumar, P.I., and Chattopadhyaya, J. (2001). A critical survey of the structure-function of the antisense oligo/RNA heteroduplex as substrate for RNase H. J Biochem Biophys Methods 48, 189-208.