Abstract
Telomeres and telomerase are nowadays exploring traits on targets for anticancer therapy. Telomerase is a unique reverse transcriptase enzyme, considered as a primary factor in almost all cancer cells, which is mainly responsible to regulate the telomere length. Hence, telomerase ensures the indefinite cell proliferation during malignancy—a hallmark of cancer—and this distinctive feature has provided telomerase as the preferred target for drug development in cancer therapy. Deactivation of telomerase and telomere destabilization by natural products provides an opening to succeed new targets for cancer therapy. This review aims to provide a fundamental knowledge for research on telomere, working regulation of telomerase and its various binding proteins to inhibit the telomere/telomerase complex. In addition, the review summarizes the inhibitors of the enzyme catalytic subunit and RNA component, natural products that target telomeres, and suppression of transcriptional and post-transcriptional levels. This extensive understanding of telomerase biology will provide indispensable information for enhancing the efficiency of rational anti-cancer drug design.
Highlights
Telomerase was initially investigated in the transformed cervical carcinoma (HeLa) cell line in 1989 [1]
This study has further demonstrated that colorectal cancer has a close relationship with Human telomerase reverse transcriptase (hTERT) mRNA expression and high telomerase activity
Telomerase is a diagnostic and therapeutic biomarker because it is absent from most somatic cells and is present in most cancer cells
Summary
Telomerase was initially investigated in the transformed cervical carcinoma (HeLa) cell line in 1989 [1]. Telomerase is a ribonucleic reverse transcriptase enzyme, which reimburses for the loss of those telomeric sequences by connecting tandem repeats at the 3 end of chromosomes, which produce the telomeres. This enzyme adds nucleotide repeats to telomeres by using RNA template providing karyotype stability and compensating for the loss of DNA replication [4]. Telomeres are sequenced by short pattern tandem repetitions of hexanucleotide (TTAGGG) in all eukaryotic organisms. They are essential components that stabilize the ends of eukaryotic chromosome and avoid the loss of genetic information [6]. Telomeres normally help to control the proliferative capacity of normal somatic cells [7]
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