Tbilisi State University, Georgia
Title: Epigenetic regulation of function of aged chromatin
Dr.Teimuraz Lezhava is a professor at Tbilisi State University his research interest is on Epigentics.
Topotecan (a novel topoisomerase I inhibitor and a water-soluble camptothecin analog) is active against numerous human tumor cell lines, and has shown promising antineoplastic activity in solid tumors and acute leukemia. Due to the primary dose-limiting toxicity of topotecan which is myelosuppression, it is necessary to identify other chemotherapeutic agents that can work synergistically with topotecan, potentially increasing its efficacy while limiting its toxicity. Many studies showed synergism upon combination of topotecan with other chemotherapeutic agents like Gemcitabine, bortezomin and CP-4055. Other studies report the increase in growth inhibition of gemcitabine or oxaliplatin when cells are pre-exposed to naturally occurring drugs such as thymoquinone. Objective:
The aim of this project is to study the mode of action of topotecan, in comparison with thymoquinone, on survival and apoptosis pathways in AML cell lines, and to investigate the potential synergistic effect of thymoquinone on the anti-tumor activity of the chemotherapeutic agent topotecan. The analysis of obtained results showed: 1. Chromosome progressive heterocromatinization (of eu- and heterochromatin regions) occurs at aging; 2. Decrease of repair processes and increase in frequency of chromosome aberration in aging are secondary to the progressive heterochromatinization. Chromosome heterochromatinization is a key factor of aging; 3. Chromosome heterochromatinization may be the reason for some senile pathologies (peptide bioregulators Ala-Glu; Asp-Gly; Lys-Glu-Asp-Ala and Lys-Glu induces deheterochromatinization - decondensation of total heterochromatin); 4. Chromosome heterochromatinization is an area where one should seek the ways for prolonging the lifespan.