Investigation of the Enyzmatic Interactions Between Roxithromycin and DNA Topoisomerase I and II
Abstract
drugs. The reasons underlying this unique priority are that topoisomerase enzymes are indispensable for the cell's own life dynamics, in the synthesis of RNA and proteins in the cell, or more importantly, for the preservation of genetic material. These enzymes are similar in terms of structure and functionality in many living groups, and by having relatively similar activities, they enable the creation of controlled DNA breaks and the reunification of DNA fragments in the cell. In fact, they are a kind of problem solver regarding the use of narrow spaces with their activities that enable the separation of long DNA molecules, which can be considered as gigantic in size, depending on the cell area in which they are located. In our study, the anticancer activity of Roxithromycin has been evaluated by topoisomerase enzyme assay analyses. Given the growing body of evidence supporting the anticancer properties of certain antibiotics, we evaluated whether Roxithromycin has different targets than those known through its potential anticancer effects and interactions with topoisomerase enzymes. Our findings revealed that roxithromycin selectively inhibited topoisomerase II activity, but did not show any inhibitory effect on topoisomerase I.
Keywords
Topoisomerase enzymes, Anti-cancer drugs, Roxithromycin, Antibiotics.
Supporting Institution
Scientific Research Project Fund of Sivas Cumhuriyet University
Project Number
ECZ 2022-087
References
- Pommier Y., Sun Y.,. Huang S.Y. N, and Nitiss J.L., Roles of eukaryotic topoisomerases in transcription, replication and genomic stability, Nat Rev Mol Cell Biol., 11 (2016) 703-721.
- Wang, J.C., Cellular roles of DNA topoisomerases: A molecular perspective, Nat Rev Mol Cell Biol., (6) (2002) 430-440.
- Pommier Y., Leo E., Zhang H., and Marchand C., DNA topoisomerases and their poisoning by anticancer and antibacterial drugs, Chem Biol., 17 (5) (2010) 421-433.
- Nadelmann J., Francis J.H., Brodie S.E., Muca E., and Abramson D.H., Is intravitreal topotecan toxic to retinal function?, Br J Ophthalmol., 105 (7) (2021) 1016-1018.
- Sen M., Rao R., Mulay K., Reddy V.A.P., and Honavar S.G., Intravitreal Topotecan for Vitreous Seeds in Retinoblastoma, Ophthalmology, 131 (10) (2024) 1215-1224.
- Moreno L, Weston R, Owens C, Valteau-Couanet D, Gambart M, Castel V, Zwaan CM, Nysom K, Gerber N, Castellano A, Laureys G, Ladenstein R, Rössler J, Makin G, Murphy D, Morland B, Vaidya S, Thebaud E, van Eijkelenburg N, Tweddle DA, Barone G, Tandonnet J, Corradini N, Chastagner P, Paillard C, Bautista FJ, Gallego Melcon S, De Wilde B, Marshall L, Gray J, Burchill SA, Schleiermacher G, Chesler L, Peet A, Leach MO, McHugh K, Hayes R, Jerome N, Caron H, Laidler J, Fenwick N, Holt G, Moroz V, Kearns P, Gates S, Pearson ADJ, Wheatley K., Innovative Therapies for Children with Cancer (ITCC) and European Association for Neuroblastoma Research (SIOPEN). Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial, J Clin Oncol., 42 ( 10) (2024) 1135-1145.
- Upadhyayula P.S., Spinazzi E.F., Argenziano M. G., Canoll P., and Bruce J.N., Convection Enhanced Delivery of Topotecan for Gliomas: A Single-Center Experience, Pharmaceutics, 13 (1) (2020) 39.
- Baize N, Monnet I, Greillier L, Geier M, Lena H, Janicot H, Vergnenegre A, Crequit J, Lamy R, Auliac JB, Letreut J, Le Caer H, Gervais R, Dansin E, Madroszyk A, Renault PA, Le Garff G, Falchero L, Berard H, Schott R, Saulnier P, Chouaid C; Groupe Français de Pneumo-Cancérologie 01–13 investigators, Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial, Lancet Oncol., 21 (9) (2020) 1224-1233.
- Singh V., Afshan T., Tyagi P., Varadwaj P.K., and Sahoo A.K., Recent development of multi-targeted inhibitors of human topoisomerase II enzyme as potent cancer therapeutics, Int J Biol Macromol., 226, (2023) 473-484.
- Kciuk M., Gielecińska A., Mujwar S., Kołat D., Kałuzińska-Kołat Ż., Celik I., Kontek R., Doxorubicin-An Agent with Multiple Mechanisms of Anticancer Activity, Cells, 12 (4) (2023) 659.