Telomere and Telomerase: From Discovery to Cancer Treatment

Abstract

Context: Cancer is a major cause of death worldwide. It was estimated that 7.6 million people died during 2008 due to cancer and this figure is expected to double by 2030. To conquer this disease, discovery of validated targets and new drugs is a necessity. Evidence Acquisition: Telomeres are terminal structures of linear chromosomes in eukaryotes and consist of multiple repetitive sequences. Their main function is to protect and confer stability to chromosome ends and prevent their breakage, end-to-end fusion, and degeneration. Polymerases responsible for replication of DNA in eukaryotes are not able to replicate chromosome ends and, during cell division, chromosomes continuously become shorter from the telomere ends. This shortening will eventually stop cell division. In cancer cells, there is a ribonucleoprotein enzyme called telomerase that allows compensation of telomere shortening and continuation of the cell multiplication process. Results: About 90% of cancers need a high level of this enzyme to continue cell multiplication. Since this enzyme set is absent in normal cells, or present at a very low level, use of telomerase inhibitors cannot have significant effects on normal cells. Conclusions: Since telomerase is expressed in 90% of cancer cells, its inhibition can be considered as a goal of cancer treatment.

Berberine Inhibits Telomerase Activity and Induces Cell Cycle Arrest and Telomere Erosion in Colorectal Cancer Cell Line, HCT 116

“…Telomerase is highly expressed in proliferative cells, such as cancer, stem, and gamete cells, but not in normal cells [ 17 ]. However, telomerase activity is higher in cancer cells compared to most stem cells except for embryonic stem cells [ 18 ].…”

“…However, telomerase activity is higher in cancer cells compared to most stem cells except for embryonic stem cells [ 18 ]. It is challenging to determine whether telomerase inhibition will affect gamete and stem cells as cancer cells are affected; however, due to the shorter length of telomere as well as the difference of the metabolism in cancer cells, it would have undergone apoptosis even before it could adversely affect germ line and stem cells [ 17 ]. The aim of this study was to investigate the effects of telomerase inhibitor compound treatment on the cell cycle, doubling time (t d ), telomerase activity, and level as well as on the telomere length of a colorectal cancer cell line, using HCT 116 as a model.…”