Telomerase inhibitors and T-oligo' as cancer therapeutics: Contrasting molecular mechanisms of cytotoxicity

Anti-Cancer Drugs

Volumn 19, Issue 4, 2008, Pages 329-338

  Rankin, Andrew M ^a   Faller, Douglas V ^a   Spanjaard, Remco A ^a  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

2 5A antisense oligonucleotides; BIBR1532; BRACO 19; G quadruplex interacting ligands; GRN163L; Nucleoside analogs; Peptide nucleic acids; Telomestatin; Thio phosphoramidates

Indexed keywords

ANTINEOPLASTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; AZYDOTHYMIDINE; AZYDOTHYMIDINE TRIPHOSPHATE; BIBR 1532; BIBR 1563; BRACO 19; DIDEOXYGUANOSINE; DNA; GRN 163; GRN 163L; NUCLEOSIDE ANALOG; PEPTIDE NUCLEIC ACID; TELOMERASE INHIBITOR; TELOMESTATIN; UNCLASSIFIED DRUG; ACRIDINE DERIVATIVE; AMINOBENZOIC ACID DERIVATIVE; BRACO19; ENZYME INHIBITOR; GRN163; NAPHTHALENE DERIVATIVE; OLIGONUCLEOTIDE; TELOMERASE;

ACUTE GRANULOCYTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; B CELL LYMPHOMA; BREAST CANCER; CANCER THERAPY; CELL AGING; CELL PROLIFERATION; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL TRIAL; DNA DAMAGE; DRUG CYTOTOXICITY; DRUG EXPOSURE; DRUG MECHANISM; ENDOMETRIUM CARCINOMA; EXPERIMENTAL MODEL; GENE OVEREXPRESSION; GENOMIC INSTABILITY; GLIOBLASTOMA; HUMAN; LIVER CELL CARCINOMA; LUNG CANCER; LUNG CARCINOMA; LUNG NON SMALL CELL CANCER; MOLECULAR MECHANICS; MOLECULAR MIMICRY; MULTIPLE CANCER; MULTIPLE MYELOMA; NONHODGKIN LYMPHOMA; NONHUMAN; OVARY CANCER; OVARY CARCINOMA; PRIORITY JOURNAL; PROLYMPHOCYTIC LEUKEMIA; PROSTATE CANCER; PROSTATE CARCINOMA; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; SEQUENCE HOMOLOGY; SOMATIC CELL; T CELL LEUKEMIA; TELOMERE; ANIMAL; CELL CULTURE; DRUG ANTAGONISM; ENZYMOLOGY; GENETICS; NEOPLASM; PHYSIOLOGY;

ACRIDINES; AMINOBENZOIC ACIDS; ANIMALS; ANTINEOPLASTIC AGENTS; ENZYME INHIBITORS; HUMANS; NAPHTHALENES; NEOPLASMS; OLIGONUCLEOTIDES; OLIGONUCLEOTIDES, ANTISENSE; TELOMERASE; TELOMERE; TUMOR CELLS, CULTURED;

EID: 47949115565     PISSN: 09594973     EISSN: None     Source Type: Journal    
DOI: 10.1097/CAD.0b013e3282f5d4c2     Document Type: Review

References (67)

1. Nicol Keith W, Jeffry Evans TR, Glasspool RM. Telomerase and cancer: time to move from a promising target to a clinical reality. J Pathol 2001; 195:404-414.
2. Meyerson M. Role of telomerase in normal and cancer cells. J Clin Oncol 2000; 18:2626-2634.
3. Wright WE, Pereira-Smith OM, Shay JW. Reversible cellular senescence: implications for immortalization of normal human diploid fibroblasts. Mol Cell Biol 1989; 9:3088-3092.
4. Blackburn EH. Telomere states and Cell fates. Nature 2000; 408:53-56.
5. Shay JW, Wright WE, Werbin H. Defining the molecular mechanisms of human Cell immortalizations. Biochim Biophys Acta 1991; 1072:1-7.
6. Shay JW, Pereira-Smith OM, Wright WE. Role for both Rb and P53 in the regulation of human cellular senescence. Exp Cell Res 1991; 196:33-39.
7. Shay JW, Wright WE. Telomerase therapeutics for cancer: challenges and new directions. Nat Rev Drug Discov 2006; 5:577-584.
8. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, et al. Specific association of human telomerase activity with immortal cells and cancer. Science 1994; 266:2011-2015.
9. Bisoffi M, Heaphy CM, Griffith JK. Telomeres: prognostic markers for solid tumors. Int J Cancer 2006; 119:2255-2260.
10. De Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 2005; 19:2100-2110.
11. Smogorzewska A, de Lange T. Regulation of telomerase by telomere proteins. Annu Rev Biochem 2004; 73:177-208.
12. De Lange T. Protection of mammalian telomeres. Oncogene 2002; 21: 532-540.
13. Wu L, Multani AS, He H, Cosme-Blanco W, Deng Y, Deng JM, et al. Pot1 deficiency initiates DNA damage checkpoint activation and aberrant homologous recombination at telomeres. Cell 2006; 126:49-62.
14. Verdun RE, Karlseder J. Replication and protection of human telomeres. Nature 2007; 447:924-931.
15. Ferreira MG, Miller KM, Cooper JP. Indecent exposure: when telomeres become uncapped. Mol Cell 2004; 13:7-18.
16. Takai H, Smogorzewska A, de Lange T. DNA damage foci at dysfunctional telomeres. Curr Biol 2003; 13:1549-1556.
17. Zhu XD, Niedernhofer L, Kuster B, Mann M, Hoeijmakers JH, de Lange T. ERCC1-XPF removes the 3′ overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes. Mol Cell 2003; 12:1489-1498.
18. Crabbe L, Jauch A, Naeger CM, Holtgreve-Grez H, Karlseder J. Telomere dysfunction as a cause of genetic instability in Werner syndrome. Proc Natl Acad Sci U S A 2007; 104:2205-2210.
19. Opresko PL, Cheng WH, von Kobbe C, Harrigan JA, Bohr VA. Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process. Carcinogenesis 2003; 24:791-802.
20. Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, et al. Extension of life-span by introduction of telomerase into normal human cells. Science 1998; 279:349-352.
21. Vaziri H, Benchimol S. Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span. Curr Biol 1998; 8:279-282.
22. Halvorsen TL, Leibowitz G, Levine F. Telomerase activity is sufficient to allow transformed cells to escape from crisis. Mol Cell Biol 1999; 19:1864-1870.
23. Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 1997; 91:25-34.
24. González-Suárez E, Samper E, Flores JM, Blasco MA. Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis. Nat Genet 2000; 26:114-117.
25. Wang K, Zhang QF, Wang XS, Xue YW, Pang D, Fu SB. Peptide nucleic acids arrest the growth of gastric cancer cells SGC7901. Chin Med J 2004; 117:566-570.
26. Shammas MA, Simmons CG, Corey DR, Schmookler Reis RJ. Telomerase inhibition by peptide nucleic acids reverses immortality of transformed human cells. Oncogene 1999; 18:6191-6200.
27. Villa R, Folini M, Lualdi S, Veronese S, Daidone MG, Zaffaronia N. Inhibition of telomerase activity by a cell-penetrating peptide nucleic acid construct in human melanoma cells. FEBS Lett 2000; 473:241-248.
28. Kondo S, Kondo Y, Li G, Silverman RH, Cowell JK. Targeted therapy of human malignant glioma in a mouse model by 2-5A antisense directed against telomerase RNA. Oncogene 1998; 16: 3323-3330.
29. Mukai S, Kondo Y, Koga S, Komata T, Barna BP, Kondo S. 2-5A antisense telomerase RNA therapy for intracranial malignant gliomas. Cancer Res 2000; 60:4461-4467.
30. Koga S, Kondo Y, Komata T, Kondo S. Treatment of bladder cancer cells in vitro and in vivo with 2-5A antisense telomerase RNA. Gene Ther 2001; 8:654-658.
31. Herbert BS, Pongracz K, Shay JW, Gryaznov SM. Oligonucleotide N3′-P5′ phosphoramidates as efficient telomerase inhibitors. Oncogene 2002; 21:638-642.
32. Akiyama M, Hideshima T, Shammas MA, Hayashi T, Hamasaki M, Tai YT, et al. Effects of oligonucleotide N3′→P5′ thio-phosphoramidate (GRN163) targeting telomerase RNA in human multiple myeloma cells. Cancer Res 2003; 63:6187-6194.
33. Asai A, Oshima Y, Yamamoto Y, Uochi T, Kusaka H, Akinaga S. A novel telomerase template antagonist (GRN163) as a potential anticancer agent. Cancer Res 2003; 63:3931-3939.
34. Ozawa T, Gryaznov SM, Hu LJ, Pongracz K, Santos RA, Bollen AW, et al. Antitumor effects of specific telomerase inhibitor GRN163 in human glioblastoma xenografts. Neuro-oncol 2004; 6:218-226.
35. Wang ES, Wu K, Chin AC, Chen-Kiang S, Pongracz K, Gryaznov S, et al. Telomerase inhibition with an oligonucleotide telomerase template antagonist: in vitro and in vivo studies in multiple myeloma and lymphoma. Blood 2004; 103:258-266.
36. Herbert BS, Gellert GC, Hochreiter A, Pongracz K, Wright WE, Zielinska D, et al. Lipid modification of GRN163, an N3′→P5′ thio-phosphoramidate oligonucleotide, enhances the potency of telomerase inhibition. Oncogene 2005; 24:5262-5268.
37. Dikmen ZG, Gellert GC, Jackson S, Gryaznov S, Tressler R, Dogan P, et al. In vivo inhibition of lung cancer by GRN163L: a novel human telomerase inhibitor. Cancer Res 2005; 65:7866-7873.
38. Hochreiter AE, Xiao H, Goldblatt EM, Gryaznov SM, Miller KD, Badve S, et al. Telomerase template antagonist GRN163L disrupts telomere maintenance, tumor growth, and metastasis of breast cancer. Clin Cancer Res 2006; 12:3184-3192.
39. Djojosubroto MW, Chin AC, Go N, Schaetzlein S, Manns MP, Gryaznov S, et al. Telomerase antagonists GRN163 and GRN163L inhibit tumor growth and increase chemosensitivity of human hepatoma. Hepatology 2005; 42:1127-1136.
40. Fletcher TM, Cathers BE, Ravikumar KS, Mamiya BM, Kerwin SM. Inhibition of human telomerase by 7-deaza-2′-deoxyguanosine nucleoside triphosphate analogs: potent inhibition by 6-thio-7-deaza-2′ -deoxyguanosine 5′-triphosphate. Bioorg Chem 2001; 29:36-55.
41. Murakami J, Nagai N, Shigemasa K, Ohama K. Inhibition of telomerase activity and Cell proliferation by a reverse transcriptase inhibitor in gynaecological cancer Cell lines. Eur J Cancer 1999; 35:1027-1034.
42. Melana SM, Holland JF, Pogo BG. Inhibition of Cell growth and telomerase activity of breast cancer in vitro by 3′-azido-3′- deoxythymidine. Clin Cancer Res 1998; 4:693-696.
43. Strahl C, Blackburn EH. Effects of reverse transcriptase inhibitors on telomere length and telomerase activity in two immortalized human Cell lines. Mol Cell Biol 1996; 16:53-65.
44. Pascolo E, Wenz C, Lingner J, Hauel N, Priepke H, Kauffmann I, et al. Mechanism of human telomerase inhibition by BIBR1532, a synthetic, non-nucleosidic drug candidate. J Biol Chem 2002; 277:15566-15572.
45. Damm K, Hemmann U, Garin-Chesa P, Hauel N, Kauffmann I, Priepke H, et al. A highly selective telomerase inhibitor limiting human cancer proliferation. EMBO J 2001; 20:6958-6968.
46. El-Daly H, Kull M, Zimmermann S, Pantic M, Waller CF, Martens UM. Selective cytotoxicity and telomere damage in leukemia cells using the telomerase inhibitor BIBR1532. Blood 2005; 105:1742-1749.
47. Incles CM, Schultes CM, Kempski H, Koehler H, Kelland LR, Neidle S. A G-quadruplex telomere targeting agent produces p16-associated senescence and chromosomal fusions in human prostate cancer cells. Mol Cancer Ther 2004; 3:1201-1206.
48. Gunaratnam M, Greciano O, Martins C, Reszka AP, Schultes CM, Morjani H, et al. Mechanism of acridine-based telomerase inhibition and telomere shortening. Biochem Pharmacol 2007; 74:679-689.
49. Burger AM, Dai F, Schultes CM, Reszka AP, Moore MJ, Double JA, et al. The G-quadruplex-interactive molecule BRACO-19 inhibits tumor growth, consistent with telomere targeting and interference with telomerase function. Cancer Res 2005; 65:1489-1496.
50. Gomez D, Paterski R, Lemarteleur T, Shin-Ya K, Mergny JL, Riou JF. Interaction of telomestatin with the telomeric single-strand overhang. J Biol Chem 2004; 279:41487-41494.
51. Gomez D, Wenner T, Brassart B, Douarre C, O'Donohue MF, El Khoury V, et al. Telomestatin-induced telomere uncapping is modulated by Pot1 through G-overhang extension in HT1080 human tumor cells. J Biol Chem 2006; 281:38721-38729.
52. Eller MS, Puri N, Hadshiew IM, Venna SS, Gilchrest BA. Induction of apoptosis by telomere 3′ overhang specific DNA. Exp Cell Res 2002; 276:185-193.
53. Van Steensel B, Smogorzewska A, de Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell 1998; 92:401-413.
54. Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T. p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 1999; 283:1321-1325.
55. Smogorzewska A, de Lange T. Different telomere damage signaling pathways in human and mouse cells. EMBO J 2002; 21:4338-4348.
56. Artandi SE, Attardi LD. Pathways connecting telomeres and p53 in senescence, apoptosis, and cancer. Biochem Biophys Res Commun 2005; 331:881-890.
57. Yaar M, Eller MS, Panova I, Kubera J, Wee LH, Cowan KH, et al. Telomeric DNA induces differentiation, apoptosis, and senescence of human breast carcinoma cells. Breast Cancer Res 2007; 9:R13.
58. Li GZ, Eller MS, Hanna K, Gilchrest BA. Signaling pathway requirements for induction of senescence by telomere homolog oligonucleotides. Exp Cell Res 2004; 301:189-200.
59. Lim DS, Kim ST, Xu B, Maser RS, Lin J, Petrini JH, et al. ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway. Nature 2000; 404:613-617.
60. Eller MS, Li GZ, Firoozabadi R, Puri N, Gilchrest BA. Induction of a p95/ Nbs-1-mediated S phase checkpoint by telomere 3′ overhang specific DNA. FASEB J 2003; 2:152-162.
61. Canman CE, Lim DS, Cimprich KA, Taya Y, Tamai K, Sakaguchi K, et al. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 1998; 281:1677-1679.
62. Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 2001; 6:42462-42467.
63. Ahn JY, Schwarz JK, Piwnica-Worms H, Canman CE. Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation. Cancer Res 2000; 60:5934-5936.
64. Eller MS, Liao X, Liu S, Hanna K, Bäckvall H, Opresko PL, et al. A role for WRN in telomere-based DNA damage responses. Proc Natl Acad Sci U S A 2006; 103:15073-15078.
65. Aoki H, Iwado E, Eller MS, Kondo Y, Fujiwara K, Li GZ, et al. Telomere 3′ overhang-specific DNA oligonucleotides induce autophagy in malignant glioma cells. FASEB J 2007; 21:2918-2930.
66. Puri N, Eller MS, Byers HR, Dykstra S, Kubera J, Gilchrest BA. Telomere-based DNA damage responses: a new approach to melanoma. FASEB J 2004; 18:1373-1381.
67. Longe HO, Romesser PB, Faller DV, Eller MS, Gilchrest BA, Sinha A, et al. Telomere DNA-based adjunctive therapy is effective for lymphoid malignancy. Proc Am Assoc Cancer Res 2007; abstract 1216.