| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
1 Cancer Research UK Biomolecular Structure Group, School of Pharmacy, University of London, London, United Kingdom; 2 Institute of Child Health, London, United Kingdom; and 3 Antisoma Research Laboratories, St. George's Hospital Medical School, London, United Kingdom
Requests for reprints: Stephen Neidle, Cancer Research UK Biomolecular Structure Group, School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom. Phone: 44-207-753-5969; Fax: 44-207-753-5970. E-mail: stephen.neidle{at}ulsop.ac.uk
The trisubstituted acridine derivative BRACO-19 has been designed to interact with and stabilize the quadruplex DNA structures that can be formed by folding of the single-stranded repeats at the 3' end of human telomeres. We suggest that the BRACO-19 complex inhibits the catalytic function of telomerase in human cancer cells and also destabilizes the telomerase-telomere capping complex so that cells enter senescence. Here, we present evidence showing that the inhibition of cell growth caused by BRACO-19 in DU145 prostate cancer cells occurs more rapidly than would be expected solely by the inhibition of the catalytic function of telomerase, and that senescence is accompanied by an initial up-regulation of the cyclin-dependent kinase inhibitor p21, with subsequent increases in p16INK4a expression. We also show that treatment with BRACO-19 causes extensive end-to-end chromosomal fusions, consistent with telomere uncapping.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
4 C. Incles and H. Koehler, unpublished observations.
5 C. Gerner and S. Neidle, unpublished observations.
Received 4/ 2/04; revised 7/13/04; accepted 8/20/04.
This article has been cited by other articles:
|
|
 |
|
  G. Pennarun, C. Granotier, F. Hoffschir, E. Mandine, D. Biard, L. R. Gauthier, and F. D. Boussin Role of ATM in the telomere response to the G-quadruplex ligand 360A Nucleic Acids Res., March 1, 2008; 36(5): 1741 - 1754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. K. Yadav, J. K. Abraham, P. Mani, R. Kulshrestha, and S. Chowdhury QuadBase: genome-wide database of G4 DNA occurrence and conservation in human, chimpanzee, mouse and rat promoters and 146 microbes Nucleic Acids Res., January 11, 2008; 36(suppl_1): D381 - D385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Patel, A. T. Phan, and V. Kuryavyi Human telomere, oncogenic promoter and 5'-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics Nucleic Acids Res., December 3, 2007; 35(22): 7429 - 7455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Brassart, D. Gomez, A. D. Cian, R. Paterski, A. Montagnac, K.-H. Qui, N. Temime-Smaali, C. Trentesaux, J.-L. Mergny, F. Gueritte, et al. A New Steroid Derivative Stabilizes G-Quadruplexes and Induces Telomere Uncapping in Human Tumor Cells Mol. Pharmacol., September 1, 2007; 72(3): 631 - 640. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Kelland Targeting the Limitless Replicative Potential of Cancer: The Telomerase/Telomere Pathway Clin. Cancer Res., September 1, 2007; 13(17): 4960 - 4963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Qi, C.-P. Lin, X. Fu, L. M. Wood, A. A. Liu, Y.-C. Tsai, Y. Chen, C. M. Barbieri, D. S. Pilch, and L. F. Liu G-Quadruplexes Induce Apoptosis in Tumor Cells Cancer Res., December 15, 2006; 66(24): 11808 - 11816. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Rawal, V. B. R. Kummarasetti, J. Ravindran, N. Kumar, K. Halder, R. Sharma, M. Mukerji, S. K. Das, and S. Chowdhury Genome-wide prediction of G4 DNA as regulatory motifs: Role in Escherichia coli global regulation. Genome Res., May 1, 2006; 16(5): 644 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Cookson, F. Dai, V. Smith, R. A. Heald, C. A. Laughton, M. F. G. Stevens, and A. M. Burger Pharmacodynamics of the G-Quadruplex-Stabilizing Telomerase Inhibitor 3,11-Difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate (RHPS4) in Vitro: Activity in Human Tumor Cells Correlates with Telomere Length and Can Be Enhanced, or Antagonized, with Cytotoxic Agents Mol. Pharmacol., December 1, 2005; 68(6): 1551 - 1558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Granotier, G. Pennarun, L. Riou, F. Hoffschir, L. R. Gauthier, A. De Cian, D. Gomez, E. Mandine, J.-F. Riou, J.-L. Mergny, et al. Preferential binding of a G-quadruplex ligand to human chromosome ends Nucleic Acids Res., July 28, 2005; 33(13): 4182 - 4190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Douarre, D. Gomez, H. Morjani, J.-M. Zahm, M.-F. O'Donohue, L. Eddabra, P. Mailliet, J.-F. Riou, and C. Trentesaux Overexpression of Bcl-2 is associated with apoptotic resistance to the G-quadruplex ligand 12459 but is not sufficient to confer resistance to long-term senescence Nucleic Acids Res., April 14, 2005; 33(7): 2192 - 2203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Burger, F. Dai, C. M. Schultes, A. P. Reszka, M. J. Moore, J. A. Double, and S. Neidle The G-Quadruplex-Interactive Molecule BRACO-19 Inhibits Tumor Growth, Consistent with Telomere Targeting and Interference with Telomerase Function Cancer Res., February 15, 2005; 65(4): 1489 - 1496. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
