Telomere maintenance as a target for drug discovery

Journal of Medicinal Chemistry

Volumn 57, Issue 3, 2014, Pages 521-538

  Sekaran, Vijay ^a   Soares, Joana ^a   Jarstfer, Michael B ^a  

^a University of North Carolina   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG DELIVERY SYSTEMS; G-QUADRUPLEXES; GENE TRANSFER TECHNIQUES; HUMANS; IMMUNOTHERAPY; MOLECULAR TARGETED THERAPY; NEOPLASMS; TELOMERASE; TELOMERE; TRANSCRIPTION, GENETIC;

EID: 84890811542     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm400528t     Document Type: Review

References (221)

1. Shay, J. W.; Bacchetti, S. A survey of telomerase activity in human cancer Eur. J. Cancer 1997, 33, 787-791
2. Beatty, G. L.; Vonderheide, R. H. Telomerase as a universal tumor antigen for cancer vaccines Expert Rev. Vaccines 2008, 7, 881-887
3. Fujiwara, T.; Urata, Y.; Tanaka, N. Telomerase-specific oncolytic virotherapy for human cancer with the hTERT promoter Curr. Cancer Drug Targets 2007, 7, 191-201
4. Jakupciak, J. P. Real-time telomerase activity measurements for detection of cancer Expert Rev. Mol. Diagn. 2005, 5, 745-753
5. Deng, Y.; Chan, S. S.; Chang, S. Telomere dysfunction and tumour suppression: the senescence connection Nat. Rev. Cancer 2008, 8, 450-458
6. Palm, W.; de Lange, T. How shelterin protects mammalian telomeres Annu. Rev. Genet. 2008, 42, 301-334
7. Sperka, T.; Wang, J.; Rudolph, K. L. DNA damage checkpoints in stem cells, ageing and cancer Nat. Rev. Mol. Cell Biol. 2012, 13, 579-590
8. Moon, I. K.; Jarstfer, M. B. The human telomere and its relationship to human disease, therapy, and tissue engineering Front. Biosci. 2007, 12, 4595-4620
9. Blasco, M. A. Telomeres and human disease: ageing, cancer and beyond Nat. Rev. Genet. 2005, 6, 611-622
10. Collins, K. The biogenesis and regulation of telomerase holoenzymes Nat. Rev. Mol. Cell Biol. 2006, 7, 484-494
11. Sekaran, V. G.; Soares, J.; Jarstfer, M. B. Structures of telomerase subunits provide functional insights Biochim. Biophys. Acta 2010, 1804, 1190-1201
12. Feng, J.; Funk, W. D.; Wang, S. S.; Weinrich, S. L.; Avilion, A. A.; Chiu, C. P.; Adams, R. R.; Chang, E.; Allsopp, R. C.; Yu, J.; Le, S.; West, M. D.; Harley, C.; Andrews, W. H.; Greider, C. W.; Villeponteu, B. The RNA component of human telomerase Science 1995, 269, 1236-1241
13. Nakamura, T. M.; Morin, G. B.; Chapman, K. B.; Weinrich, S. L.; Andrews, W. H.; Lingner, J.; Harley, C. B.; Cech, T. R. Telomerase catalytic subunit homologs from fission yeast and human Science 1997, 277, 955-959
14. Huang, F. W.; Hodis, E.; Xu, M. J.; Kryukov, G. V.; Chin, L.; Garraway, L. A. Highly recurrent TERT promoter mutations in human melanoma Science 2013, 339, 957-959
15. Karlseder, J.; Smogorzewska, A.; de Lange, T. Senescence induced by altered telomere state, not telomere loss Science 2002, 295, 2446-2449
16. Griffith, J. D.; Comeau, L.; Rosenfield, S.; Stansel, R. M.; Bianchi, A.; Moss, H.; de Lange, T. Mammalian telomeres end in a large duplex loop Cell 1999, 97, 503-514
17. Cao, Y.; Bryan, T. M.; Reddel, R. R. Increased copy number of the TERT and TERC telomerase subunit genes in cancer cells Cancer Sci. 2008, 99, 1092-1099
18. Cesare, A. J.; Reddel, R. R. Telomere uncapping and alternative lengthening of telomeres Mech. Ageing Dev. 2008, 129, 99-108
19. Muntoni, A.; Reddel, R. R. The first molecular details of ALT in human tumor cells Hum. Mol. Genet. 2005, 14, R191-R196
20. Hahn, W. C.; Counter, C. M.; Lundbeg, A. S.; Beijersbergen, R. L.; Brooks, M. W.; Weinberg, R. A. Creation of human tumour cells with defined genetic elements Nature 1999, 400, 464-468
21. Aubert, G.; Lansdorp, P. M. Telomeres and aging Physiol. Rev. 2008, 88, 557-579
22. Bollmann, F. M. The many faces of telomerase: emerging extratelomeric effects BioEssays 2008, 30, 728-732
23. Artandi, S. E.; DePinho, R. A. Telomeres and telomerase in cancer Carcinogenesis 2010, 31, 9-18
24. Xu, L.; Li, S.; Stohr, B. A. The role of telomere biology in cancer Annu. Rev. Pathol. 2013, 8, 49-78
25. Ju, Z.; Rudolph, K. L. Telomeres and telomerase in cancer stem cells Eur. J. Cancer 2006, 42, 1197-1203
26. Armanios, M.; Greider, C. W. Telomerase and cancer stem cells Cold Spring Harbor Symp. Quant. Biol. 2005, 70, 205-208
27. Kim, N. W.; Piatyszek, M. A.; Prowse, K. R.; Harley, C. B.; West, M. D.; Ho, P. L.; Coviello, G. M.; Wright, W. E.; Weinrich, S. L.; Shay, J. W. Specific association of human telomerase activity with immortal cells and cancer Science 1994, 266, 2011-2015
28. Svenson, U.; Roos, G. Telomere length as a biological marker in malignancy Biochim. Biophys. Acta 2009, 1792, 317-323
29. Hahn, W. C.; Stewart, S. A.; Brooks, M. W.; York, S. G.; Eaton, E.; Kurachi, A.; Beijersbergen, R. L.; Knoll, J. H. M.; Maeyerson, M.; Weinberg, R. A. Inhibition of telomerase limits the growth of human cancer cells Nat. Med. 1999, 5, 1164-1170
30. Zhang, X.; Mar, V.; Zhou, W.; Harrington, L.; Robinson, M. O. Telomere shortening and apoptosis in telomerase-inhibited human tumor cells Genes Dev. 1999, 13, 2388-2399
31. Roth, A.; Harley, C. B.; Baerlocher, G. M. Imetelstat (GRN163L)-telomerase-based cancer therapy Recent Results Cancer Res. 2010, 184, 221-234
32. Wong, H. M.; Payet, L.; Huppert, J. L. Function and targeting of G-quadruplexes Curr. Opin. Mol. Ther. 2009, 11, 146-155
33. Monchaud, D.; Teulade-Fichou, M. P. A hitchhiker's guide to G-quadruplex ligands Org. Biomol. Chem. 2008, 6, 627-636
34. Kyo, S.; Takakura, M.; Fujiwara, T.; Inoue, M. Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers Cancer Sci. 2008, 99, 1528-1538
35. Nemunaitis, J.; Tong, A. W.; Nemunaitis, M.; Senzer, N.; Phadke, A. P.; Bedell, C.; Adams, N.; Zhang, Y. A.; Maples, P. B.; Chen, S.; Pappen, B.; Burke, J.; Ichimaru, D.; Urata, Y.; Fujiwara, T. A phase I study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors Mol. Ther. 2010, 18, 429-434
36. Liu, J. P.; Chen, W.; Schwarer, A. P.; Li, H. Telomerase in cancer immunotherapy Biochim. Biophys. Acta, Rev. Cancer 2010, 1805, 35-42
37. Damm, K.; Hemmann, U.; Garin-Chesa, P.; Hauel, N.; Kauffmann, I.; Priepke, H.; Niestroj, C.; Daiber, C.; Enenkel, B.; Guilliard, B.; Lauritsch, I.; Muller, E.; Pascolo, E.; Sauter, G.; Pantic, M.; Martens, U. M.; Wenz, C.; Lingner, J.; Kraut, N.; Rettig, W. J.; Schnapp, A. A highly selective telomerase inhibitor limiting human cancer cell proliferation EMBO J. 2001, 20, 6958-6968
38. Huffman, K. E.; Levene, S. D.; Tesmer, V. M.; Shay, J. W.; Wright, W. E. Telomere shortening is proportional to the size of the G-rich telomeric 3′-overhang J. Biol. Chem. 2000, 275, 19719-19722
39. Zou, Y.; Sfeir, A.; Gryaznov, S. M.; Shay, J. W.; Wright, W. E. Does a sentinel or a subset of short telomeres determine replicative senescence? Mol. Biol. Cell 2004, 15, 3709-3718
40. de Lange, T. Shelterin: the protein complex that shapes and safeguards human telomeres Genes Dev. 2005, 19, 2100-2110
41. Hu, J.; Hwang, S. S.; Liesa, M.; Gan, B.; Sahin, E.; Jaskelioff, M.; Ding, Z.; Ying, H.; Boutin, A. T.; Zhang, H.; Johnson, S.; Ivanova, E.; Kost-Alimova, M.; Protopopov, A.; Wang, Y. A.; Shirihai, O. S.; Chin, L.; DePinho, R. A. Antitelomerase therapy provokes ALT and mitochondrial adaptive mechanisms in cancer Cell 2012, 148, 651-663
42. Folini, M.; Zaffaroni, N. Targeting telomerase by antisense-based approaches: perspectives for new anti-cancer therapies Curr. Pharm. Des. 2005, 11, 1105-1117
43. Cong, Y.; Shay, J. W. Actions of human telomerase beyond telomeres Cell Res. 2008, 18, 725-732
44. Park, J. I.; Venteicher, A. S.; Hong, J. Y.; Choi, J.; Jun, S.; Shkreli, M.; Chang, W.; Meng, Z.; Cheung, P.; Ji, H.; McLaughlin, M.; Veenstra, T. D.; Nusse, R.; McCrea, P. D.; Artandi, S. E. Telomerase modulates Wnt signalling by association with target gene chromatin Nature 2009, 460, 66-72
45. Ghosh, A.; Saginc, G.; Leow, S. C.; Khattar, E.; Shin, E. M.; Yan, T. D.; Wong, M.; Zhang, Z.; Li, G.; Sung, W. K.; Zhou, J.; Chng, W. J.; Li, S.; Liu, E.; Tergaonkar, V. Telomerase directly regulates NF-kappaB-dependent transcription Nat. Cell Biol. 2012, 14, 1270-1281
46. De Cian, A.; Lacroix, L.; Douarre, C.; Temime-Smaali, N.; Trentesaux, C.; Riou, J. F.; Mergny, J. L. Targeting telomeres and telomerase Biochimie 2008, 90, 131-155
47. Salvati, E.; Leonetti, C.; Rizzo, A.; Scarsella, M.; Mottolese, M.; Galati, R.; Sperduti, I.; Stevens, M. F.; D'Incalci, M.; Blasco, M.; Chiorino, G.; Bauwens, S.; Horard, B.; Gilson, E.; Stoppacciaro, A.; Zupi, G.; Biroccio, A. Telomere damage induced by the G-quadruplex ligand RHPS4 has an antitumor effect J. Clin. Invest. 2007, 117, 3236-3247
48. Miyazaki, T.; Pan, Y.; Joshi, K.; Purohit, D.; Hu, B.; Demir, H.; Mazumder, S.; Okabe, S.; Yamori, T.; Viapiano, M.; Shin-ya, K.; Seimiya, H.; Nakano, I. Telomestatin impairs glioma stem cell survival and growth through the disruption of telomeric G-quadruplex and inhibition of the proto-oncogene, c-Myb Clin. Cancer Res. 2012, 18, 1268-1280
49. Gong, Y.; de Lange, T. A Shld1-controlled POT1a provides support for repression of ATR signaling at telomeres through RPA exclusion Mol. Cell 2010, 40, 377-387
50. Melana, S. M.; Holland, J. F.; Pogo, B. G. Inhibition of cell growth and telomerase activity of breast cancer cells in vitro by 3′-azido-3′- deoxythymidine Clin. Cancer Res. 1998, 4, 693-696
51. Strahl, C.; Blackburn, E. H. Effects of reverse transcriptase inhibitors on telomere length and telomerase activity in two immortalized human cell lines Mol. Cell. Biol. 1996, 16, 53-65
52. Datta, A.; Bellon, M.; Sinha-Datta, U.; Bazarbachi, A.; Lepelletier, Y.; Canioni, D.; Waldmann, T. A.; Hermine, O.; Nicot, C. Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence Blood 2006, 108, 1021-1029
53. Johnston, J. S.; Johnson, A.; Gan, Y.; Wientjes, M. G.; Au, J. L. Synergy between 3′-azido-3′-deoxythymidine and paclitaxel in human pharynx FaDu cells Pharm. Res. 2003, 20, 957-961
54. Yasuda, C.; Kato, M.; Kuroda, D.; Ohyanagi, H. Experimental studies on potentiation of the antitumor activity of 5-fluorouracil with 3′-azido-3′-deoxythymidine for the gastric cancer cell line MKN28 in vivo Jpn. J. Cancer Res 1997, 88, 97-102
55. Chen, C.; Zhang, Y.; Wang, Y.; Huang, D.; Xi, Y.; Qi, Y. Synergic effect of 3′-azido-3′-deoxythymidine and arsenic trioxide in suppressing hepatoma cells Anti-Cancer Drugs 2011, 22, 435-443
56. Hukezalie, K. R.; Thumati, N. R.; Cote, H. C.; Wong, J. M. In vitro and ex vivo inhibition of human telomerase by anti-HIV nucleoside reverse transcriptase inhibitors (NRTIs) but not by non-NRTIs PLoS One 2012, 7, e47505
57. Leeansyah, E.; Cameron, P. U.; Solomon, A.; Tennakoon, S.; Velayudham, P.; Gouillou, M.; Spelman, T.; Hearps, A.; Fairley, C.; Smit de, V.; Pierce, A. B.; Armishaw, J.; Crowe, S. M.; Cooper, D. A.; Koelsch, K. K.; Liu, J. P.; Chuah, J.; Lewin, S. R. Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging J. Infect. Dis. 2013, 207, 1157-1165
58. Fletcher, T. M.; Cathers, B. E.; Ravikumar, K. S.; Mamiya, B. M.; Kerwin, S. M. 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
59. Hayakawa, N.; Nozawa, K.; Ogawa, A.; Kato, N.; Yoshida, K.; Akamatsu, K.; Tsuchiya, M.; Nagasaka, A.; Yoshida, S. Isothiazolone derivatives selectively inhibit telomerase from human and rat cancer cells in vitro Biochemistry 1999, 38, 11501-11507
60. Kim, J. H.; Lee, G. E.; Lee, J. E.; Chung, I. K. Potent inhibition of human telomerase by nitrostyrene derivatives Mol. Pharmacol. 2003, 63, 1117-1124
61. Kim, J. H.; Lee, G. E.; Kim, S. W.; Chung, I. K. Identification of a quinoxaline derivative that is a potent telomerase inhibitor leading to cellular senescence of human cancer cells Biochem. J. 2003, 373, 523-529
62. Gillis, A. J.; Schuller, A. P.; Skordalakes, E. Structure of the Tribolium castaneum telomerase catalytic subunit TERT Nature 2008, 455, 633-637
63. Liu, X. H.; Li, J.; Shi, J. B.; Song, B. A.; Qi, X. B. Design and synthesis of novel 5-phenyl- N -piperidine ethanone containing 4,5-dihydropyrazole derivatives as potential antitumor agents Eur. J. Med. Chem. 2012, 51, 294-299
64. Liu, X. H.; Ruan, B. F.; Liu, J. X.; Song, B. A.; Jing, L. H.; Li, J.; Yang, Y.; Zhu, H. L.; Qi, X. B. Design and synthesis of N -phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential antitumor agents Bioorg. Med. Chem. Lett. 2011, 21, 2916-2920
65. Luo, Y.; Zhang, S.; Qiu, K. M.; Liu, Z. J.; Yang, Y. S.; Fu, J.; Zhong, W. Q.; Zhu, H. L. Synthesis, biological evaluation, 3D-QSAR studies of novel aryl-2 H -pyrazole derivatives as telomerase inhibitors Bioorg. Med. Chem. Lett. 2013, 23, 1091-1095
66. Liu, X. H.; Liu, H. F.; Chen, J.; Yang, Y.; Song, B. A.; Bai, L. S.; Liu, J. X.; Zhu, H. L.; Qi, X. B. Synthesis and molecular docking study of novel coumarin derivatives containing 4,5-dihydropyrazole moiety as potential antitumor agents Bioorg. Med. Chem. Lett. 2010, 20, 5705-5708
67. Zheng, Q. Z.; Zhang, X. M.; Xu, Y.; Cheng, K.; Jiao, Q. C.; Zhu, H. L. Synthesis, biological evaluation, and molecular docking studies of 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety as potential antitumor agents Bioorg. Med. Chem. 2010, 18, 7836-7841
68. Sun, J.; Zhu, H.; Yang, Z. M.; Zhu, H. L. Synthesis, molecular modeling and biological evaluation of 2-aminomethyl-5-(quinolin-2-yl)-1,3,4-oxadiazole- 2(3 H)-thione quinolone derivatives as novel anticancer agent Eur. J. Med. Chem. 2013, 60, 23-28
69. Huang, P. R.; Yeh, Y. M.; Wang, T. C. Potent inhibition of human telomerase by helenalin Cancer Lett. 2005, 227, 169-174
70. Soares, J.; Keppler, B. R.; Wang, X.; Lee, K. H.; Jarstfer, M. B. Ortho-quinone tanshinones directly inhibit telomerase through an oxidative mechanism mediated by hydrogen peroxide Bioorg. Med. Chem. Lett. 2011, 21, 7474-7478
71. Chen, Y. J.; Sheng, W. Y.; Huang, P. R.; Wang, T. C. Potent inhibition of human telomerase by U-73122 J. Biomed. Sci. 2006, 13, 667-674
72. Ueno, T.; Takahashi, H.; Oda, M.; Mizunuma, M.; Yokoyama, A.; Goto, Y.; Mizushina, Y.; Sakaguchi, K.; Hayashi, H. Inhibition of human telomerase by rubromycins: implication of spiroketal system of the compounds as an active moiety Biochemistry 2000, 39, 5995-6002
73. Mizushina, Y.; Ueno, T.; Oda, M.; Yamaguchi, T.; Saneyoshi, M.; Sakaguchi, K. The biochemical mode of inhibition of DNA polymerase beta by alpha-rubromycin Biochim. Biophys. Acta 2000, 1523, 172-181
74. Nakai, R.; Ishida, H.; Asai, A.; Ogawa, H.; Yamamoto, Y.; Kawasaki, H.; Akinaga, S.; Mizukami, T.; Yamashita, Y. Telomerase inhibitors identified by a forward chemical genetics approach using a yeast strain with shortened telomere length Chem. Biol. 2006, 13, 183-190
75. Uchida, K.; Ogawa, T.; Yasuda, Y.; Mimura, H.; Fujimoto, T.; Fukuyama, T.; Wakimoto, T.; Asakawa, T.; Hamashima, Y.; Kan, T. Stereocontrolled total synthesis of (+)-UCS1025A Angew. Chem. 2012, 51, 12850-12853
76. Lambert, T. H.; Danishefsky, S. J. Total synthesis of UCS1025A J. Am. Chem. Soc. 2006, 128, 426-427
77. Wong, L. H.; Unciti-Broceta, A.; Spitzer, M.; White, R.; Tyers, M.; Harrington, L. A yeast chemical genetic screen identifies inhibitors of human telomerase Chem. Biol. 2013, 20, 333-340
78. Barma, D. K.; Elayadi, A.; Falck, J. R.; Corey, D. R. Inhibition of telomerase by BIBR 1532 and related analogues Bioorg. Med. Chem. Lett. 2003, 13, 1333-1336
79. Pascolo, E.; Wenz, C.; Lingner, J.; Hauel, N.; Priepke, H.; Kauffmann, I.; Garin-Chesa, P.; Rettig, W. J.; Damm, K.; Schnapp, A. Mechanism of human telomerase inhibition by BIBR1532, a synthetic, non-nucleosidic drug candidate J. Biol. Chem. 2002, 277, 15566-15572
80. El-Daly, H.; Kull, M.; Zimmermann, S.; Pantic, M.; Waller, C. F.; Martens, U. M. Selective cytotoxicity and telomere damage in leukemia cells using the telomerase inhibitor BIBR1532 Blood 2005, 105, 1742-1749
81. Ward, R. J.; Autexier, C. Pharmacological telomerase inhibition can sensitize drug-resistant and drug-sensitive cells to chemotherapeutic treatment Mol. Pharmacol. 2005, 68, 779-786
82. Pantic, M.; Zimmermann, S.; Waller, C. F.; Martens, U. M. The level of telomere dysfunction determines the efficacy of telomerase-based therapeutics in a lung cancer cell line Int. J. Cancer 2005, 26, 1227-1232
83. Hamilton, S. E.; Simmons, C. G.; Kathiriya, I. S.; Corey, D. R. Cellular delivery of peptide nucleic acids and inhibition of human telomerase Chem. Biol. 1999, 6, 343-351
84. Keppler, B. R.; Jarstfer, M. B. Inhibition of telomerase activity by preventing proper assemblage Biochemistry 2004, 43, 334-343
85. Pinto, I. G.; Guilbert, C.; Ulyanov, N. B.; Stearns, J.; James, T. L. Discovery of ligands for a novel target, the human telomerase RNA, based on flexible-target virtual screening and NMR J. Med. Chem. 2008, 51, 7205-7215
86. Dominick, P. K.; Keppler, B. R.; Legassie, J. D.; Moon, I. K.; Jarstfer, M. B. Nucleic acid-binding ligands identify new mechanisms to inhibit telomerase Bioorg. Med. Chem. Lett. 2004, 14, 3467-3471
87. Kaiser, M.; Sainlos, M.; Lehn, J. M.; Bombard, S.; Teulade-Fichou, M. P. Aminoglycoside-quinacridine conjugates: towards recognition of the P6.1 element of telomerase RNA ChemBioChem 2006, 7, 321-329
88. Jain, N.; Francis, S.; Friedman, S. H. Inhibition of therapeutically important polymerases with high affinity bis-intercalators Bioorg. Med. Chem. Lett. 2012, 22, 4844-4848
89. Rangarajan, S.; Friedman, S. H. Design, synthesis, and evaluation of phenanthridine derivatives targeting the telomerase RNA/DNA heteroduplex Bioorg. Med. Chem. Lett. 2007, 17, 2267-2273
90. Meyerson, M.; Counter, C. M.; Eaton, E. N.; Ellisen, L. W.; Steiner, P.; Caddle, S. D.; Ziaugra, L.; Beijersbergen, R. L.; Davidoff, M. J.; Liu, Q.; Bacchetti, S.; Haber, D. A.; Weinberg, R. A. hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization Cell 1997, 90, 785-795
91. Cong, Y. S.; Wen, J.; Bacchetti, S. The human telomerase catalytic subunit hTERT: organization of the gene and characterization of the promoter Hum. Mol. Genet. 1999, 8, 137-142
92. Grandori, C.; Cowley, S. M.; James, L. P.; Eisenman, R. N. The Myc/Max/Mad network and the transcriptional control of cell behavior Annu. Rev. Cell Dev. Biol. 2000, 16, 653-699
93. Moon, D. O.; Kim, M. O.; Lee, J. D.; Choi, Y. H.; Kim, G. Y. Butein suppresses c-Myc-dependent transcription and Akt-dependent phosphorylation of hTERT in human leukemia cells Cancer Lett. 2009, 286, 172-179
94. Guo, Q. L.; Lin, S. S.; You, Q. D.; Gu, H. Y.; Yu, J.; Zhao, L.; Qi, Q.; Liang, F.; Tan, Z.; Wang, X. Inhibition of human telomerase reverse transcriptase gene expression by gambogic acid in human hepatoma SMMC-7721 cells Life Sci. 2006, 78, 1238-1245
95. Jagadeesh, S.; Kyo, S.; Banerjee, P. P. Genistein represses telomerase activity via both transcriptional and posttranslational mechanisms in human prostate cancer cells Cancer Res. 2006, 66, 2107-2115
96. Shapira, S.; Granot, G.; Mor-Tzuntz, R.; Raanani, P.; Uziel, O.; Lahav, M.; Shpilberg, O. Second-generation tyrosine kinase inhibitors reduce telomerase activity in K562 cells Cancer Lett. 2012, 323, 223-231
97. Wooten, L. G.; Ogretmen, B. Sp1/Sp3-dependent regulation of human telomerase reverse transcriptase promoter activity by the bioactive sphingolipid ceramide J. Biol. Chem. 2005, 280, 28867-28876
98. Kyo, S.; Takakura, M.; Taira, T.; Kanaya, T.; Itoh, H.; Yutsudo, M.; Ariga, H.; Inoue, M. Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT) Nucleic Acids Res. 2000, 28, 669-677
99. Misiti, S.; Nanni, S.; Fontemaggi, G.; Cong, Y. S.; Wen, J.; Hirte, H. W.; Piaggio, G.; Sacchi, A.; Pontecorvi, A.; Bacchetti, S.; Farsetti, A. Induction of hTERT expression and telomerase activity by estrogens in human ovary epithelium cells Mol. Cell. Biol. 2000, 20, 3764-3771
100. Kyo, S.; Takakura, M.; Kanaya, T.; Zhuo, W.; Fujimoto, K.; Nishio, Y.; Orimo, A.; Inoue, M. Estrogen activates telomerase Cancer Res. 1999, 59, 5917-5921
101. Nanni, S.; Narducci, M.; Della Pietra, L.; Moretti, F.; Grasselli, A.; De Carli, P.; Sacchi, A.; Pontecorvi, A.; Farsetti, A. Signaling through estrogen receptors modulates telomerase activity in human prostate cancer J. Clin. Invest. 2002, 110, 219-227
102. Aldous, W. K.; Marean, A. J.; DeHart, M. J.; Matej, L. A.; Moore, K. H. Effects of tamoxifen on telomerase activity in breast carcinoma cell lines Cancer 1999, 85, 1523-1529
103. Wang, Z.; Kyo, S.; Takakura, M.; Tanaka, M.; Yatabe, N.; Maida, Y.; Fujiwara, M.; Hayakawa, J.; Ohmichi, M.; Koike, K.; Inoue, M. Progesterone regulates human telomerase reverse transcriptase gene expression via activation of mitogen-activated protein kinase signaling pathway Cancer Res. 2000, 60, 5376-5381
104. Xu, D.; Popov, N.; Hou, M.; Wang, Q.; Bjorkholm, M.; Gruber, A.; Menkel, A. R.; Henriksson, M. Switch from Myc/Max to Mad1/Max binding and decrease in histone acetylation at the telomerase reverse transcriptase promoter during differentiation of HL60 cells Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 3826-3831
105. Gunes, C.; Lichtsteiner, S.; Vasserot, A. P.; Englert, C. Expression of the hTERT gene is regulated at the level of transcriptional initiation and repressed by Mad1 Cancer Res. 2000, 60, 2116-2121
106. Kanaya, T.; Kyo, S.; Hamada, K.; Takakura, M.; Kitagawa, Y.; Harada, H.; Inoue, M. Adenoviral expression of p53 represses telomerase activity through down-regulation of human telomerase reverse transcriptase transcription Clin. Cancer Res. 2000, 6, 1239-1247
107. Crowe, D. L.; Nguyen, D. C. Rb and E2F-1 regulate telomerase activity in human cancer cells Biochim. Biophys. Acta 2001, 1518, 1-6
108. Henderson, Y. C.; Breau, R. L.; Liu, T. J.; Clayman, G. L. Telomerase activity in head and neck tumors after introduction of wild-type p53, p21, p16, and E2F-1 genes by means of recombinant adenovirus Head Neck 2000, 22, 347-354
109. Oh, S.; Song, Y.; Yim, J.; Kim, T. K. The Wilms' tumor 1 tumor suppressor gene represses transcription of the human telomerase reverse transcriptase gene J. Biol. Chem. 1999, 274, 37473-37478
110. Lindkvist, A.; Ivarsson, K.; Jernberg-Wiklund, H.; Paulsson-Karlsson, Y. Interferon-induced sensitization to apoptosis is associated with repressed transcriptional activity of the hTERT promoter in multiple myeloma Biochem. Biophys. Res. Commun. 2006, 341, 1141-1148
111. Lacerte, A.; Korah, J.; Roy, M.; Yang, X. J.; Lemay, S.; Lebrun, J. J. Transforming growth factor-beta inhibits telomerase through SMAD3 and E2F transcription factors Cell. Signalling 2008, 20, 50-59
112. Li, H.; Xu, D.; Li, J.; Berndt, M. C.; Liu, J. P. Transforming growth factor beta suppresses human telomerase reverse transcriptase (hTERT) by Smad3 interactions with c-Myc and the hTERT gene J. Biol. Chem. 2006, 281, 25588-25600
113. Fujiki, T.; Miura, T.; Maura, M.; Shiraishi, H.; Nishimura, S.; Imada, Y.; Uehara, N.; Tashiro, K.; Shirahata, S.; Katakura, Y. TAK1 represses transcription of the human telomerase reverse transcriptase gene Oncogene 2007, 26, 5258-5266
114. Terme, J. M.; Mocquet, V.; Kuhlmann, A. S.; Zane, L.; Mortreux, F.; Wattel, E.; Duc Dodon, M.; Jalinot, P. Inhibition of the hTERT promoter by the proto-oncogenic protein TAL1 Leukemia 2009, 23, 2081-2089
115. Wu, P.; Meng, L.; Wang, H.; Zhou, J.; Xu, G.; Wang, S.; Xi, L.; Chen, G.; Wang, B.; Zhu, T.; Lu, Y.; Ma, D. Role of hTERT in apoptosis of cervical cancer induced by histone deacetylase inhibitor Biochem. Biophys. Res. Commun. 2005, 335, 36-44
116. Woo, H. J.; Lee, S. J.; Choi, B. T.; Park, Y. M.; Choi, Y. H. Induction of apoptosis and inhibition of telomerase activity by trichostatin A, a histone deacetylase inhibitor, in human leukemic U937 cells Exp. Mol. Pathol. 2007, 82, 77-84
117. Choi, Y. H. Apoptosis of U937 human leukemic cells by sodium butyrate is associated with inhibition of telomerase activity Int. J. Oncol. 2006, 29, 1207-1213
118. Won, J.; Chang, S.; Oh, S.; Kim, T. K. Small-molecule-based identification of dynamic assembly of E2F-pocket protein-histone deacetylase complex for telomerase regulation in human cells Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 11328-11333
119. Berletch, J. B.; Liu, C.; Love, W. K.; Andrews, L. G.; Katiyar, S. K.; Tollefsbol, T. O. Epigenetic and genetic mechanisms contribute to telomerase inhibition by EGCG J. Cell. Biochem. 2008, 103, 509-519
120. Wang, X.; Hao, M. W.; Dong, K.; Lin, F.; Ren, J. H.; Zhang, H. Z. Apoptosis induction effects of EGCG in laryngeal squamous cell carcinoma cells through telomerase repression Arch. Pharmacal Res. 2009, 32, 1263-1269
121. Sadava, D.; Whitlock, E.; Kane, S. E. The green tea polyphenol, epigallocatechin-3-gallate inhibits telomerase and induces apoptosis in drug-resistant lung cancer cells Biochem. Biophys. Res. Commun. 2007, 360, 233-237
122. Seimiya, H.; Oh-hara, T.; Suzuki, T.; Naasani, I.; Shimazaki, T.; Tsuchiya, K.; Tsuruo, T. Telomere shortening and growth inhibition of human cancer cells by novel synthetic telomerase inhibitors MST-312, MST-295, and MST-1991 Mol. Cancer Ther. 2002, 1, 657-665
123. Bilsland, A. E.; Hoare, S.; Stevenson, K.; Plumb, J.; Gomez-Roman, N.; Cairney, C.; Burns, S.; Lafferty-Whyte, K.; Roffey, J.; Hammonds, T.; Keith, W. N. Dynamic telomerase gene suppression via network effects of GSK3 inhibition PLoS One 2009, 4, e6459
124. Pendino, F.; Flexor, M.; Delhommeau, F.; Buet, D.; Lanotte, M.; Segal-Bendirdjian, E. Retinoids down-regulate telomerase and telomere length in a pathway distinct from leukemia cell differentiation Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 6662-6667
125. Pendino, F.; Dudognon, C.; Delhommeau, F.; Sahraoui, T.; Flexor, M.; Bennaceur-Griscelli, A.; Lanotte, M.; Segal-Bendirdjian, E. Retinoic acid receptor alpha and retinoid-X receptor-specific agonists synergistically target telomerase expression and induce tumor cell death Oncogene 2003, 22, 9142-9150
126. Li, H.; Zhao, L. L.; Funder, J. W.; Liu, J. P. Protein phosphatase 2A inhibits nuclear telomerase activity in human breast cancer cells J. Biol. Chem. 1997, 272, 16729-16732
127. Kang, S. S.; Kwon, T.; Kwon, D. Y.; Do, S. I. Akt protein kinase enhances human telomerase activity through phosphorylation of telomerase reverse transcriptase subunit J. Biol. Chem. 1999, 274, 13085-13090
128. Yu, C. C.; Lo, S. C.; Wang, T. C. Telomerase is regulated by protein kinase C-zeta in human nasopharyngeal cancer cells Biochem. J. 2001, 355, 459-464
129. Kim, Y. W.; Hur, S. Y.; Kim, T. E.; Lee, J. M.; Namkoong, S. E.; Ki, I. K.; Kim, J. W. Protein kinase C modulates telomerase activity in human cervical cancer cells Exp. Mol. Med. 2001, 33, 156-163
130. Uziel, O.; Fenig, E.; Nordenberg, J.; Beery, E.; Reshef, H.; Sandbank, J.; Birenbaum, M.; Bakhanashvili, M.; Yerushalmi, R.; Luria, D.; Lahav, M. Imatinib mesylate (Gleevec) downregulates telomerase activity and inhibits proliferation in telomerase-expressing cell lines Br. J. Cancer 2005, 92, 1881-1891
131. Kharbanda, S.; Kumar, V.; Dhar, S.; Pandey, P.; Chen, C.; Majumder, P.; Yuan, Z. M.; Whang, Y.; Strauss, W.; Pandita, T. K.; Weaver, D.; Kufe, D. Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase Curr. Biol. 2000, 10, 568-575
132. Soares, J.; Lowe, M. M.; Jarstfer, M. B. The catalytic subunit of human telomerase is a unique caspase-6 and caspase-7 substrate Biochemistry 2011, 50, 9046-9055
133. Holt, S. E.; Aisner, D. L.; Baur, J.; Tesmer, V. M.; Dy, M.; Ouellette, M.; Trager, J. B.; Morin, G. B.; Toft, D. O.; Shay, J. W.; Wright, W. E.; White, M. A. Functional requirement of p23 and Hsp90 in telomerase complexes Genes Dev. 1999, 13, 817-826
134. Keppler, B. R.; Grady, A. T.; Jarstfer, M. B. The biochemical role of the heat shock protein 90 chaperone complex in establishing human telomerase activity J. Biol. Chem. 2006, 281, 19840-19848
135. Chang, J. T.; Lu, Y. C.; Chen, Y. J.; Tseng, C. P.; Chen, Y. L.; Fang, C. W.; Cheng, A. J. hTERT phosphorylation by PKC is essential for telomerase holoprotein integrity and enzyme activity in head neck cancer cells Br. J. Cancer 2006, 94, 870-878
136. Compton, S. A.; Elmore, L. W.; Haydu, K.; Jackson-Cook, C. K.; Holt, S. E. Induction of nitric oxide synthase-dependent telomere shortening after functional inhibition of Hsp90 in human tumor cells Mol. Cell. Biol. 2006, 26, 1452-1462
137. Villa, R.; Folini, M.; Porta, C. D.; Valentini, A.; Pennati, M.; Daidone, M. G.; Zaffaroni, N. Inhibition of telomerase activity by geldanamycin and 17-allylamino, 17-demethoxygeldanamycin in human melanoma cells Carcinogenesis 2003, 24, 851-859
138. Phan, A. T. Human telomeric G-quadruplex: structures of DNA and RNA sequences FEBS J. 2010, 277, 1107-1117
139. Neidle, S. Human telomeric G-quadruplex: the current status of telomeric G-quadruplexes as therapeutic targets in human cancer FEBS J 2010, 277, 1118-1125
140. Bochman, M. L.; Paeschke, K.; Zakian, V. A. DNA secondary structures: stability and function of G-quadruplex structures Nat. Rev. Genet. 2012, 13, 770-780
141. Zahler, A. M.; Williamson, J. R.; Cech, T. R.; Prescott, D. M. Inhibition of telomerase by G-quartet DNA structures Nature 1991, 350, 718-720
142. Sun, D.; Thompson, B.; Cathers, B. E.; Salazar, M.; Kerwin, S. M.; Trent, J. O.; Jenkins, T. C.; Neidle, S.; Hurley, L. H. Inhibition of human telomerase by a G-quadruplex-interactive compound J. Med. Chem. 1997, 40, 2113-2116
143. Harrison, R. J.; Gowan, S. M.; Kelland, L. R.; Neidle, S. Human telomerase inhibition by substituted acridine derivatives Bioorg. Med. Chem. Lett. 1999, 9, 2463-2468
144. Monchaud, D.; Granzhan, A.; Saettel, N.; Guedin, A.; Mergny, J. L.; Teulade-Fichou, M. P. "One ring to bind them all"-part I: the efficiency of the macrocyclic scaffold for G-quadruplex DNA recognition J. Nucleic Acids 2010, 2010, 1-19
145. Lam, E. Y.; Beraldi, D.; Tannahill, D.; Balasubramanian, S. G-quadruplex structures are stable and detectable in human genomic DNA Nat. Commun. 2013, 4, 1796
146. Palumbo, S. L.; Ebbinghaus, S. W.; Hurley, L. H. Formation of a unique end-to-end stacked pair of G-quadruplexes in the hTERT core promoter with implications for inhibition of telomerase by G-quadruplex-interactive ligands J. Am. Chem. Soc. 2009, 131, 10878-10891
147. Fernando, H.; Reszka, A. P.; Huppert, J.; Ladame, S.; Rankin, S.; Venkitaraman, A. R.; Neidle, S.; Balasubramanian, S. A conserved quadruplex motif located in a transcription activation site of the human c-kit oncogene Biochemistry 2006, 45, 7854-7860
148. Rankin, S.; Reszka, A. P.; Huppert, J.; Zloh, M.; Parkinson, G. N.; Todd, A. K.; Ladame, S.; Balasubramanian, S.; Neidle, S. Putative DNA quadruplex formation within the human c-kit oncogene J. Am. Chem. Soc. 2005, 127, 10584-10589
149. Ambrus, A.; Chen, D.; Dai, J.; Jones, R. A.; Yang, D. Solution structure of the biologically relevant G-quadruplex element in the human c-MYC promoter. Implications for G-quadruplex stabilization Biochemistry 2005, 44, 2048-2058
150. Siddiqui-Jain, A.; Grand, C. L.; Bearss, D. J.; Hurley, L. H. Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 11593-11598
151. Chen, Y.; Yang, D. Sequence, Stability, and Structure of G-Quadruplexes and Their Interactions with Drugs Curr. Protoc. Nucleic Acid Chem. 2012, 50, 17.5.1-17.5.17
152. Vy Thi Le, T.; Han, S.; Chae, J.; Park, H. J. G-quadruplex binding ligands: from naturally occurring to rationally designed molecules Curr. Pharm. Des. 2012, 18, 1948-1972
153. Perry, P. J.; Read, M. A.; Davies, R. T.; Gowan, S. M.; Reszka, A. P.; Wood, A. A.; Kelland, L. R.; Neidle, S. 2,7-Disubstituted amidofluorenone derivatives as inhibitors of human telomerase J. Med. Chem. 1999, 42, 2679-2684
154. Li, Q.; Xiang, J. F.; Yang, Q. F.; Sun, H. X.; Guan, A. J.; Tang, Y. L. G4LDB: a database for discovering and studying G-quadruplex ligands Nucleic Acids Res. 2013, 41, D1115-D1123
155. Nicoludis, J. M.; Miller, S. T.; Jeffrey, P. D.; Barrett, S. P.; Rablen, P. R.; Lawton, T. J.; Yatsunyk, L. A. Optimized end-stacking provides specificity of N -methyl mesoporphyrin IX for human telomeric G-quadruplex DNA J. Am. Chem. Soc. 2012, 134, 20446-20456
156. Li, Q.; Xiang, J. F.; Zhang, H.; Tang, Y. L. Searching drug-like anti-cancer compound(s) based on G-quadruplex ligands Curr. Pharm. Des. 2012, 18, 1973-1983
157. Bazzicalupi, C.; Ferraroni, M.; Bilia, A. R.; Scheggi, F.; Gratteri, P. The crystal structure of human telomeric DNA complexed with berberine: an interesting case of stacked ligand to G-tetrad ratio higher than 1:1 Nucleic Acids Res. 2013, 41, 632-638
158. Patel, D. J.; Phan, A. T.; Kuryavyi, V. Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics Nucleic Acids Res. 2007, 35, 7429-7455
159. Collie, G. W.; Promontorio, R.; Hampel, S. M.; Micco, M.; Neidle, S.; Parkinson, G. N. Structural basis for telomeric G-quadruplex targeting by naphthalene diimide ligands J. Am. Chem. Soc. 2012, 134, 2723-2731
160. Sparapani, S.; Haider, S. M.; Doria, F.; Gunaratnam, M.; Neidle, S. Rational design of acridine-based ligands with selectivity for human telomeric quadruplexes J. Am. Chem. Soc. 2010, 132, 12263-12272
161. Drygin, D.; Siddiqui-Jain, A.; O'Brien, S.; Schwaebe, M.; Lin, A.; Bliesath, J.; Ho, C. B.; Proffitt, C.; Trent, K.; Whitten, J. P.; Lim, J. K.; Von Hoff, D.; Anderes, K.; Rice, W. G. Anticancer activity of CX-3543: a direct inhibitor of rRNA biogenesis Cancer Res. 2009, 69, 7653-7661
162. Citti, L.; Rainaldi, G. Synthetic hammerhead ribozymes as therapeutic tools to control disease genes Curr. Gene Ther. 2005, 5, 11-24
163. Folini, M.; Colella, G.; Villa, R.; Lualdi, S.; Daidone, M. G.; Zaffaroni, N. Inhibition of telomerase activity by a hammerhead ribozyme targeting the RNA component of telomerase in human melanoma cells J. Invest. Dermatol. 2000, 114, 259-267
164. Lu, Y.; Gu, J.; Jin, D.; Gao, Y.; Yuan, M. Inhibition of telomerase activity by HDV ribozyme in cancers J. Exp. Clin. Cancer Res. 2011, 30, 1
165. Yokoyama, Y.; Takahashi, Y.; Shinohara, A.; Lian, Z.; Wan, X.; Niwa, K.; Tamaya, T. Attenuation of telomerase activity by a hammerhead ribozyme targeting the template region of telomerase RNA in endometrial carcinoma cells Cancer Res. 1998, 58, 5406-5410
166. Yeo, M.; Rha, S. Y.; Jeung, H. C.; Hu, S. X.; Yang, S. H.; Kim, Y. S.; An, S. W.; Chung, H. C. Attenuation of telomerase activity by hammerhead ribozyme targeting human telomerase RNA induces growth retardation and apoptosis in human breast tumor cells Int. J. Cancer 2005, 114, 484-489
167. Ochi, A.; Umekage, S.; Kikuchi, Y. Non-enzymatic in vitro production of circular hammerhead ribozyme targeting the template region of human telomerase RNA Nucleic Acids Symp. Ser. 2009, 275-276
168. Yokoyama, Y.; Takahashi, Y.; Shinohara, A.; Wan, X.; Takahashi, S.; Niwa, K.; Tamaya, T. The 5′-end of hTERT mRNA is a good target for hammerhead ribozyme to suppress telomerase activity Biochem. Biophys. Res. Commun. 2000, 273, 316-321
169. Hao, Z. M.; Luo, J. Y.; Cheng, J.; Li, L.; He, D.; Wang, Q. Y.; Yang, G. X. Intensive inhibition of hTERT expression by a ribozyme induces rapid apoptosis of cancer cells through a telomere length-independent pathway Cancer Biol. Ther. 2005, 4, 1098-1103
170. You, Y.; Pu, P.; Huang, Q.; Xia, Z.; Wang, C.; Wang, G.; Yu, C.; Yu, J. J.; Reed, E.; Li, Q. Q. Antisense telomerase RNA inhibits the growth of human glioma cells in vitro and in vivo Int. J. Cancer 2006, 28, 1225-1232
171. Glukhov, A. I.; Zimnik, O. V.; Gordeev, S. A.; Severin, S. E. Inhibition of telomerase activity of melanoma cells in vitro by antisense oligonucleotides Biochem. Biophys. Res. Commun. 1998, 248, 368-371
172. Tarkanyi, I.; Horvath, A.; Szatmari, I.; Eizert, H.; Vamosi, G.; Damjanovich, S.; Segal-Bendirdjian, E.; Aradi, J. Inhibition of human telomerase by oligonucleotide chimeras, composed of an antisense moiety and a chemically modified homo-oligonucleotide FEBS Lett. 2005, 579, 1411-1416
173. Ohnuma, T.; Li, F. L.; Holland, J. F. Inhibitory effects of telomere-mimic phosphorothioate oligonucleotides on various human tumor cells in vitro Anticancer Res. 1997, 17, 2455-2458
174. Mata, J. E.; Joshi, S. S.; Palen, B.; Pirruccello, S. J.; Jackson, J. D.; Elias, N.; Page, T. J.; Medlin, K. L.; Iversen, P. L. A hexameric phosphorothioate oligonucleotide telomerase inhibitor arrests growth of Burkitt's lymphoma cells in vitro and in vivo Toxicol. Appl. Pharmacol. 1997, 144, 189-197
175. Pitts, A. E.; Corey, D. R. Inhibition of human telomerase by 2′- O -methyl-RNA Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 11549-11554
176. Natarajan, S.; Chen, Z.; Wancewicz, E. V.; Monia, B. P.; Corey, D. R. Telomerase reverse transcriptase (hTERT) mRNA and telomerase RNA (hTR) as targets for downregulation of telomerase activity Oligonucleotides 2004, 14, 263-273
177. Herbert, B.; Pitts, A. E.; Baker, S. I.; Hamilton, S. E.; Wright, W. E.; Shay, J. W.; Corey, D. R. Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 14276-14281
178. Beisner, J.; Dong, M.; Taetz, S.; Piotrowska, K.; Kleideiter, E.; Friedel, G.; Schaefer, U.; Lehr, C. M.; Klotz, U.; Murdter, T. E. Efficient telomerase inhibition in human non-small cell lung cancer cells by liposomal delivery of 2′- O -methyl-RNA J. Pharm. Sci. 2009, 98, 1765-1774
179. Beisner, J.; Dong, M.; Taetz, S.; Nafee, N.; Griese, E. U.; Schaefer, U.; Lehr, C. M.; Klotz, U.; Murdter, T. E. Nanoparticle mediated delivery of 2′- O -methyl-RNA leads to efficient telomerase inhibition and telomere shortening in human lung cancer cells Lung Cancer 2010, 68, 346-354
180. Chen, Z.; Monia, B. P.; Corey, D. R. Telomerase inhibition, telomere shortening, and decreased cell proliferation by cell permeable 2′- O -methoxyethyl oligonucleotides J. Med. Chem. 2002, 45, 5423-5425
181. Chen, Z.; Koeneman, K. S.; Corey, D. R. Consequences of telomerase inhibition and combination treatments for the proliferation of cancer cells Cancer Res. 2003, 63, 5917-5925
182. Norton, J. C.; Piatyszek, M. A.; Wright, W. E.; Shay, J. W.; Corey, D. R. Inhibition of human telomerase activity by peptide nucleic acids Nat. Biotechnol. 1996, 14, 615-619
183. Harrison, J. G.; Frier, C.; Laurant, R.; Dennis, R.; Raney, K. D.; Balasubramanian, S. Inhibition of human telomerase by PNA-cationic peptide conjugates Bioorg. Med. Chem. Lett. 1999, 9, 1273-1278
184. Paranjape, J. M.; Xu, D.; Kushner, D. M.; Okicki, J.; Lindner, D. J.; Cramer, H.; Silverman, R. H.; Leaman, D. W. Human telomerase RNA degradation by 2′-5′-linked oligoadenylate antisense chimeras in a cell-free system, cultured tumor cells, and murine xenograft models Oligonucleotides 2006, 16, 225-238
185. Kondo, S.; Kondo, Y.; Li, G.; Silverman, R. H.; Cowell, J. K. Targeted therapy of human malignant glioma in a mouse model by 2-5A antisense directed against telomerase RNA Oncogene 1998, 16, 3323-3330
186. Yatabe, N.; Kyo, S.; Kondo, S.; Kanaya, T.; Wang, Z.; Maida, Y.; Takakura, M.; Nakamura, M.; Tanaka, M.; Inoue, M. 2-5A antisense therapy directed against human telomerase RNA inhibits telomerase activity and induces apoptosis without telomere impairment in cervical cancer cells Cancer Gene Ther. 2002, 9, 624-630
187. Wong, S. C.; Yu, H.; Moochhala, S. M.; So, J. B. Antisense telomerase induced cell growth inhibition, cell cycle arrest and telomerase activity down-regulation in gastric and colon cancer cells Anticancer Res. 2003, 23, 465-469
188. Mukai, S.; Kondo, Y.; Koga, S.; Komata, T.; Barna, B. P.; Kondo, S. 2-5A antisense telomerase RNA therapy for intracranial malignant gliomas Cancer Res. 2000, 60, 4461-4467
189. Asai, A.; Oshima, Y.; Yamamoto, Y.; Uochi, T. A.; Kusaka, H.; Akinaga, S.; Yamashita, Y.; Pongracz, K.; Pruzan, R.; Wunder, E.; Piatyszek, M.; Li, S.; Chin, A. C.; Harley, C. B.; Gryaznov, S. A novel telomerase template antagonist (GRN163) as a potential anticancer agent Cancer Res. 2003, 63, 3931-3939
190. Herbert, B. S.; Gellert, G. C.; Hochreiter, A.; Pongracz, K.; Wright, W. E.; Zielinska, D.; Chin, A. C.; Harley, C. B.; Shay, J. W.; Gryaznov, S. M. Lipid modification of GRN163, an N3′→P5′ thio-phosphoramidate oligonucleotide, enhances the potency of telomerase inhibition Oncogene 2005, 24, 5262-5268
191. Marian, C. O.; Cho, S. K.; McEllin, B. M.; Maher, E. A.; Hatanpaa, K. J.; Madden, C. J.; Mickey, B. E.; Wright, W. E.; Shay, J. W.; Bachoo, R. M. The telomerase antagonist, imetelstat, efficiently targets glioblastoma tumor-initiating cells leading to decreased proliferation and tumor growth Clin. Cancer Res. 2010, 16, 154-163
192. Tokcaer-Keskin, Z.; Dikmen, Z. G.; Ayaloglu-Butun, F.; Gultekin, S.; Gryaznov, S. M.; Akcali, K. C. The effect of telomerase template antagonist GRN163L on bone-marrow-derived rat mesenchymal stem cells is reversible and associated with altered expression of cyclin d1, cdk4 and cdk6 Stem Cell Rev. 2010, 6, 224-233
193. Goldblatt, E. M.; Gentry, E. R.; Fox, M. J.; Gryaznov, S. M.; Shen, C.; Herbert, B. S. The telomerase template antagonist GRN163L alters MDA-MB-231 breast cancer cell morphology, inhibits growth, and augments the effects of paclitaxel Mol. Cancer Ther. 2009, 8, 2027-2035
194. Hochreiter, A. E.; Xiao, H.; Goldblatt, E. M.; Gryaznov, S. M.; Miller, K. D.; Badve, S.; Sledge, G. W.; Herbert, B. S. Telomerase template antagonist GRN163L disrupts telomere maintenance, tumor growth, and metastasis of breast cancer Clin. Cancer Res. 2006, 12, 3184-3192
195. Dikmen, Z. G.; Gellert, G. C.; Jackson, S.; Gryaznov, S.; Tressler, R.; Dogan, P.; Wright, W. E.; Shay, J. W. In vivo inhibition of lung cancer by GRN163L: a novel human telomerase inhibitor Cancer Res. 2005, 65, 7866-7873
196. Gellert, G. C.; Dikmen, Z. G.; Wright, W. E.; Gryaznov, S.; Shay, J. W. Effects of a novel telomerase inhibitor, GRN163L, in human breast cancer Breast Cancer Res. Treat. 2006, 96, 73-81
197. Shammas, M. A.; Koley, H.; Bertheau, R. C.; Neri, P.; Fulciniti, M.; Tassone, P.; Blotta, S.; Protopopov, A.; Mitsiades, C.; Batchu, R. B.; Anderson, K. C.; Chin, A.; Gryaznov, S.; Munshi, N. C. Telomerase inhibitor GRN163L inhibits myeloma cell growth in vitro and in vivo Leukemia 2008, 22, 1410-1418
198. Dikmen, Z. G.; Wright, W. E.; Shay, J. W.; Gryaznov, S. M. Telomerase targeted oligonucleotide thio-phosphoramidates in T24-luc bladder cancer cells J. Cell. Biochem. 2008, 104, 444-452
199. George, J.; Banik, N. L.; Ray, S. K. Knockdown of hTERT and concurrent treatment with interferon-gamma inhibited proliferation and invasion of human glioblastoma cell lines Int. J. Biochem. Cell Biol. 2010, 42, 1164-1173
200. Djojosubroto, M. W.; Chin, A. C.; Go, N.; Schaetzlein, S.; Manns, M. P.; Gryaznov, S.; Harley, C. B.; Rudolph, K. L. Telomerase antagonists GRN163 and GRN163L inhibit tumor growth and increase chemosensitivity of human hepatoma Hepatology 2005, 42, 1127-1136
201. Joseph, I.; Tressler, R.; Bassett, E.; Harley, C.; Buseman, C. M.; Pattamatta, P.; Wright, W. E.; Shay, J. W.; Go, N. F. The telomerase inhibitor imetelstat depletes cancer stem cells in breast and pancreatic cancer cell lines Cancer Res. 2010, 70, 9494-9504
202. Siomi, H.; Siomi, M. C. On the road to reading the RNA-interference code Nature 2009, 457, 396-404
203. Noreen, F.; Heinrich, J.; Moelling, K. Antitumor activity of small double-stranded oligodeoxynucleotides targeting telomerase RNA in malignant melanoma cells Oligonucleotides 2009, 19, 169-178
204. Li, S.; Crothers, J.; Haqq, C. M.; Blackburn, E. H. Cellular and gene expression responses involved in the rapid growth inhibition of human cancer cells by RNA interference-mediated depletion of telomerase RNA J. Biol. Chem. 2005, 280, 23709-23717
205. Shammas, M. A.; Koley, H.; Batchu, R. B.; Bertheau, R. C.; Protopopov, A.; Munshi, N. C.; Goyal, R. K. Telomerase inhibition by siRNA causes senescence and apoptosis in Barrett's adenocarcinoma cells: mechanism and therapeutic potential Mol. Cancer 2005, 4, 24
206. Shen, Y.; Zhang, Y. W.; Zhang, Z. X.; Miao, Z. H.; Ding, J. hTERT-targeted RNA interference inhibits tumorigenicity and motility of HCT116 cells Cancer Biol. Ther. 2008, 7, 228-236
207. de Souza Nascimento, P.; Alves, G.; Fiedler, W. Telomerase inhibition by an siRNA directed against hTERT leads to telomere attrition in HT29 cells Oncol. Rep. 2006, 16, 423-428
208. Gandellini, P.; Folini, M.; Bandiera, R.; De Cesare, M.; Binda, M.; Veronese, S.; Daidone, M. G.; Zunino, F.; Zaffaroni, N. Down-regulation of human telomerase reverse transcriptase through specific activation of RNAi pathway quickly results in cancer cell growth impairment Biochem. Pharmacol. 2007, 73, 1703-1714
209. Miri-Moghaddam, E.; Deezagi, A.; Soheili, Z. S. Downregulation of telomerase activity in human promyelocytic cell line using RNA interference Ann. Hematol. 2009, 88, 1169-1176
210. Liu, X.; Huang, H.; Wang, J.; Wang, C.; Wang, M.; Zhang, B.; Pan, C. Dendrimers-delivered short hairpin RNA targeting hTERT inhibits oral cancer cell growth in vitro and in vivo Biochem. Pharmacol. 2011, 82, 17-23
211. Li, Y.; Li, M.; Yao, G.; Geng, N.; Xie, Y.; Feng, Y.; Zhang, P.; Kong, X.; Xue, J.; Cheng, S.; Zhou, J.; Xiao, L. Telomerase inhibition strategies by siRNAs against either hTR or hTERT in oral squamous cell carcinoma Cancer Gene Ther. 2011, 18, 318-325
212. Vonderheide, R. H.; Domchek, S. M.; Schultze, J. L.; George, D. J.; Hoar, K. M.; Chen, D. Y.; Stephans, K. F.; Masutomi, K.; Loda, M.; Xia, Z.; Anderson, K. S.; Hahn, W. C.; Nadler, L. M. Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes Clin. Cancer Res. 2004, 10, 828-839
213. Mizukoshi, E.; Nakamoto, Y.; Arai, K.; Yamashita, T.; Sakai, A.; Sakai, Y.; Kagaya, T.; Honda, M.; Kaneko, S. Comparative analysis of various tumor-associated antigen-specific t-cell responses in patients with hepatocellular carcinoma Hepatology 2011, 53, 1206-1216
214. Hunger, R. E.; Kernland Lang, K.; Markowski, C. J.; Trachsel, S.; Moller, M.; Eriksen, J. A.; Rasmussen, A. M.; Braathen, L. R.; Gaudernack, G. Vaccination of patients with cutaneous melanoma with telomerase-specific peptides Cancer Immunol. Immunother. 2011, 60, 1553-1564
215. Painter, R. G.; Lanson, N. A., Jr.; Jin, Z.; Park, F.; Wang, G. Conditional expression of a suicide gene by the telomere reverse transcriptase promoter for potential post-therapeutic deletion of tumorigenesis Cancer Sci. 2005, 96, 607-613
216. Koga, S.; Hirohata, S.; Kondo, Y.; Komata, T.; Takakura, M.; Inoue, M.; Kyo, S.; Kondo, S. FADD gene therapy using the human telomerase catalytic subunit (hTERT) gene promoter to restrict induction of apoptosis to tumors in vitro and in vivo Anticancer Res. 2001, 21, 1937-1943
217. Kazhdan, I.; Marciniak, R. A. Death receptor 4 (DR4) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) Cancer Gene Ther. 2004, 11, 691-698
218. Zhang, Q.; Kim, N. K.; Peterson, R. D.; Wang, Z.; Feigon, J. Structurally conserved five nucleotide bulge determines the overall topology of the core domain of human telomerase RNA Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 18761-18768
219. Leeper, T. C.; Varani, G. The structure of an enzyme-activating fragment of human telomerase RNA RNA 2005, 11, 394-403
220. Steczkiewicz, K.; Zimmermann, M. T.; Kurcinski, M.; Lewis, B. A.; Dobbs, D.; Kloczkowski, A.; Jernigan, R. L.; Kolinski, A.; Ginalski, K. Human telomerase model shows the role of the TEN domain in advancing the double helix for the next polymerization step Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 9443-9448
221. Sauerwald, A.; Sandin, S.; Cristofari, G.; Scheres, S. H.; Lingner, J.; Rhodes, D. Structure of active dimeric human telomerase Nat. Struct. Mol. Biol. 2013, 20, 454-460