Telomerase Inhibition and Cancer: Might Platinum Based Drugs Have a Future as Anti-Telomerase Pharmacological Approach?
Pp. 562-586 (25)
Donato Colangelo and Domenico Osella
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 nonspecific 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.
Telomerase, telomere, antiproliferative agents, platinum(II) complexes
Dipartimento di Scienze Mediche, Universita degli Studi del Piemonte Orientale “A. Avogadro”, Via Solaroli, 17, I-28100 Novara, Italy.