INNOVATIVE ANTICANCER THERAPEUTICS BY TARGETING TELOMERES AND TELOMERASE
B. Ramya Sree
Department of Biotechnology, Sree Vidyanikethan Engineering College, Tirupati
Jyothi M. Joy
Department of Pharmacognosy, Sree Vidyanikethan College of Pharmacy, Tirupati
Telomeres are composed of many 5′-TTAGGG-3′ repetitive nucleotide sequences at each end of eukaryotic chromosomes and the cellular reverse transcriptase telomerase, an RNA-dependent DNA polymerase that adds telomeric DNA to telomeres. Telomerase is over expressed in 80-95% of cancers. Therefore telomerase activity is very important for cancer treatment. Inhibition of telomerase may lead to a decrease of telomere length resulting in cellular senescence and apoptosis in telomerase positive tumors. Long-term treatment with G-quadruplex stabilizers induces a gradual reduction in the length of the G-rich 3′ end of the telomere without a reduction of the total telomere length, suggesting that telomerase activity is inhibited. Targeting the telomere by the use of guanine-rich oligonucleotides (GROs) homologous to the 3′ telomere overhang sequence (T-oligos) have been shown to induce DNA damage responses (DDRs) such as senescence, apoptosis, and cell cycle arrest in numerous cancer cell. The loss of telomeres is an important tumor suppressor mechanism that is commonly absent in transformed malignant cells, and hence, T-oligos have garnered significant interest as a novel strategy to combat cancer. However, little is known about their mechanism of action. In this review we discuss the current understanding of how T-oligos exert their antiproliferative effects in cancer cells and their role in inhibition of telomerase. We also discuss the current understanding of telomerase in cancer and various therapeutic targets related to the telomeres and telomerase.
7 , 2 , 2017
49 - 63