Targetin g Human Tel omerase by Antisens e Oligonucleotides and Ribozymes

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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5 - Year: 2.849

Targetin g Human Tel omerase by Antisens e Oligonucleotides and Ribozymes



Anti-Cancer Agents in Medicinal Chemistry, 2(5): 605-612.

Author(s): M. Folini, M. Pennati and N Zaffaroni.

Affiliation: Dipartimento di OncologiaSperimentale, Unita' Operativa 10, Istituto Nazionale per lo Studio e la Curadei Tumori, Via Venezian 1, 20133 Milano, Italy

Abstract

Human telomerase is a ribonucleoprotein enzyme complex that enables cells to maintain telomere length, allowing indefinite replicative capacity. The notion that telomerase is reactivated in 80-90% of human cancers has led to the proposal of telomerase as a promising therapeutic target for novel anticancer interventions. Due to its inherent accessibility to nucleic acids, telomerase appears an ideal target for strategies based on the use of antisense oligonucleotides and ribozymes that target its RNA template. In this review a summary of the different antisense- and ribozyme-based approaches used thus far to inhibit telomerase activity in human cancer cells is provided. All these strategies significantly inhibited the enzyme ’ s catalytic activity in in vitro and in vivo tumor models. However, while in some studies tumor cell growth arrest was observed as a consequence of telomere shortening after prolonged telomerase inhibition, other studies have shown that antisense- and ribozyme-based treatments targeting telomerase induced rapid loss (i.e. within a few days) of tumor cell viability with concomitant apoptosis. In the latter case it is unlikely that cell death was related to telomere erosion since the cells would not have undergone enough divisions to significantly shorten their telomeres. A possible explanation is that telomerase inhibitors may induce apoptosis in cancer cells directly by interfering with the capping function of the enzyme. Overall, the available results indicate antisense oligonucleotides and ribozymes as good tools to inhibit telomerase and suggest that abrogation of telomerase activity may affect tumor cell proliferation also through pathways that are not dependent on telomere erosion.

Keywords:

Human Telomerase, Antisense Oligonucleotides, Ribozymes.



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Article Details

Volume: 2
Issue Number: 5
First Page: 605
Last Page: 612
Page Count: 8
DOI: 10.2174/1568011023353813
Price: $58
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