Abstract
Telomerase is a ribonucleoprotein polymerase that maintains the length of telomeric DNA by adding hexameric units (TTAGGG) to the ends of the chromosomes. This mechanism prevents replicative senescence, thus conferring unlimited proliferative potential to cells. Telomerase reactivation has been detected in most human tumour tissue, indicating that the enzyme may be useful as a specific tumour marker. The inhibition of telomerase causes a progressive and critical reduction of telomeres, leading to a potent signal for the blockage of cell proliferation and the induction of apoptosis. Since normal somatic cells lack telomerase activity, the anti-telomerase approach is highly specific for tumour cells and metastases. Prolonged treatment is required before enzyme deactivation causes the telomeres to be shortened enough to induce senescence and apoptosis. Therefore, the drugs employed in anti-telomerase therapy should be of only moderate non-specific cytotoxicity. Certain cis-Pt(II)-complexes have recently been shown to be effective inhibitors of telomerase in both cell-free and in vitro assays, most likely by targeting the nucleobases of the RNA component of the enzyme.
Keywords: Telomerase, telomere, antiproliferative agents, platinum(II) complexes
Current Medicinal Chemistry
Title: Telomerase Inhibition and Cancer: Might Platinum Based Drugs have a Future as Anti-telomerase Pharmacological Approach?
Volume: 12 Issue: 26
Author(s): Donato Colangelo and Domenico Osella
Affiliation:
Keywords: Telomerase, telomere, antiproliferative agents, platinum(II) complexes
Abstract: Telomerase is a ribonucleoprotein polymerase that maintains the length of telomeric DNA by adding hexameric units (TTAGGG) to the ends of the chromosomes. This mechanism prevents replicative senescence, thus conferring unlimited proliferative potential to cells. Telomerase reactivation has been detected in most human tumour tissue, indicating that the enzyme may be useful as a specific tumour marker. The inhibition of telomerase causes a progressive and critical reduction of telomeres, leading to a potent signal for the blockage of cell proliferation and the induction of apoptosis. Since normal somatic cells lack telomerase activity, the anti-telomerase approach is highly specific for tumour cells and metastases. Prolonged treatment is required before enzyme deactivation causes the telomeres to be shortened enough to induce senescence and apoptosis. Therefore, the drugs employed in anti-telomerase therapy should be of only moderate non-specific cytotoxicity. Certain cis-Pt(II)-complexes have recently been shown to be effective inhibitors of telomerase in both cell-free and in vitro assays, most likely by targeting the nucleobases of the RNA component of the enzyme.
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Cite this article as:
Colangelo Donato and Osella Domenico, Telomerase Inhibition and Cancer: Might Platinum Based Drugs have a Future as Anti-telomerase Pharmacological Approach?, Current Medicinal Chemistry 2005; 12 (26) . https://dx.doi.org/10.2174/092986705774933416
DOI https://dx.doi.org/10.2174/092986705774933416 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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