title: Pterostilbene as a potential novel telomerase inhibitor: molecular docking studies and its in vitro evaluation.
abstract: Pterostilbene is a naturally occurring dimethyl ether analog of resveratrol identified in several plant species. Telomerase is important in tumor initiation and cellular immortalization. Given the striking correlations between telomerase activity and proliferation capacity in tumor cells, telomerase had been considered as a potentially important molecular target in cancer therapeutics. Molecular docking studies were performed on pterostilbene with the crystal structure of telomerase (3DU6). Pterostilbene was evaluated for its in vitro cytotoxicity in breast (MCF7) and lung cancer (NCI H-460) cell lines, antimitotic activity in green grams and telomerase activity. Curcumin was used as a standard. Docking results indicated good interaction between pterostilbene and the active site of telomerase and the docked energy of pterostilbene was -7.10 kcal/mol. Pterostilbene showed strong inhibitory effect on in vitro telomerase activity and cell growth in both the cell lines tested in a dose dependent manner. Cancer cells treated with 80 µM pterostilbene exhibited significant telomerase inhibition, after 72 hours (MCF-7 and NCI H-460; 81.52% and 74.69% reduction, respectively, compared to control). The IC50 of pterostilbene for anti-proliferative activity in MCF7 and NCI H-460 cell lines were found to be 30.0 and 47.2 µM, respectively. The best antimitotic activity was obtained with 80 μM of pterostilbene (100% reduction in water imbibition). All the above results were comparable to that of curcumin. The drug-related properties of pterostilbene were calculated using Molinspiration, Osiris Property Explorer and ACD/Chemsketch softwares. Pterostilbene obeyed Lipinski's Rule of Five indicating its therapeutic potential in humans. It was found that the telomerase inhibitory activity exhibited by pterostilbene was dependent of the cell viability and has the potential to be a new drug candidate against breast and lung cancers.
authors.forename: Radhika
authors.initials: R
authors.lastname: Tippani
authors.forename: Laxmi Jaya Shankar
authors.initials: LJ
authors.lastname: Prakhya
authors.forename: Mahendar
authors.initials: M
authors.lastname: Porika
authors.forename: Kalam
authors.initials: K
authors.lastname: Sirisha
authors.forename: Sadanandam
authors.initials: S
authors.lastname: Abbagani
authors.affiliation: Department of Biotechnology, Kakatiya University, Warangal 506 009, Andhra Pradesh, India. tcreuben@gmail.com.
authors.forename: Christopher
authors.initials: C
authors.lastname: Thammidala
mesh_terms: D050256:Antimitotic Agents / Q000737:chemistry / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007887:Fabaceae / Q000187:drug effects; D018525:Germination / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D011485:Protein Binding; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D050256:Antimitotic Agents; D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; C107773:pterostilbene; D019098:Telomerase