Telomerase Inhibitors from Natural Products and Their Anticancer Potential

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.

Efficacy and Mechanism of Traditional Medicinal Plants and Bioactive Compounds against Clinically Important Pathogens

“…These metabolites offer clues to manufacture new structural types of antimicrobial and antifungal chemicals that are comparatively safe to humans [62]. The classes of secondary metabolites that have greater antimicrobial properties are flavonoids (flavones, flavonols, flavanols, isoflavones, anthocyanidins), phenolic acids (hydroxybenzoic, hydroxycinnamic acids), stilbenes, lignans, quinones, tannins, coumarins (simple coumarins, furanocoumarins, pyranocoumarins), terpenoids (sesquiterpene lactones, diterpenes, triterpenes, polyterpenes), alkaloids, glycosides, saponins, lectins, steroids, and polypeptides [6,16,56,62,[73][74][75][76][77][78][79][80][81][82][83]. These compounds have copious mechanisms that underlie antimicrobial activity, e.g., disturbing microbial membranes, weakening cellular metabolism, control biofilm formation, inhibiting bacterial capsule production, attenuating bacterial virulence by controlling quorum-sensing, and reducing microbial toxin production [3][4][5][6][73][74][75][76][77][78][79][80][81][82][83][84][85].…”

Long‐term in vitro treatment with telomerase inhibitor MST‐312 induces resistance by selecting long telomeres cells

“…However, strong side effects and resistance are commonly reported as responsible for failure of cancer treatment. 4,5 Telomerase is an enzyme composed of two main core subunits-hTR (RNA template subunit) and hTERT (catalytic subunit) responsible for telomere length maintenance by compensating its shortening caused by DNA replication during each cell cycle. 3 Then, telomerase inhibition has become a new potential therapeutic approach.…”

“…3 Then, telomerase inhibition has become a new potential therapeutic approach. 4,5 Telomerase is an enzyme composed of two main core subunits-hTR (RNA template subunit) and hTERT (catalytic subunit) responsible for telomere length maintenance by compensating its shortening caused by DNA replication during each cell cycle. 6 Whereas this enzyme is generally absent in normal cells and plays a crucial role in tumour ones, it is a good target for new drugs development.…”

Wild Medicinal Fungi: Phallus Impudicus-induced Telomere Damage Triggers p21/p53 and p16-dependent Cell Cycle Arrest and Drives to Male Fertility Reduction in Vitro

“…Of note, we observed an increase in TRF1 and TRF2 protein synthesis in both cell lines tested, which was probably associated with telomere shortening and numerous DNA damage at the chromosome ends. Previous reports found that natural products reduce the telomerase activity suggesting that they can be utilized as a functional food in cancer prevention (Ganesan and Xu 2017). In turn, it was reported that anti-tumor properties are associated with polysaccharides, glucomannans, which ultimately may lead to apoptosis by activation of proapoptotic protein and caspase-dependent pathways (Wasser 2002).…”