Bacterial amidohydrolases and modified 5-fluorocytidine compounds: Novel enzyme-prodrug pairs

• Published in: PloS one Vol. 18; no. 11; p. e0294696
• Main Authors: PreitakaitÄ, Viktorija, Barasa, Povilas, AucynaitÄ, Agota, Plakys, Gediminas, KoplunaitÄ, Martyna, ZubaviciutÄ, Simona, Meskys, Rolandas
• Format: Journal Article
• Language: English
• Published: San Francisco, CA USA Public Library of Science 30-11-2023; Public Library of Science (PLoS)
• Subjects: Bacteria; Biology and Life Sciences; Cancer; Care and treatment; Chemical properties; Colon cancer; Enzymes; Genes; Hydrolases; Medicine and Health Sciences; Physical Sciences; Properties; Research and Analysis Methods; Scientific equipment and supplies industry; Lithuania; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0294696

Gene-directed enzyme prodrug therapy is an emerging strategy for cancer treatment based on the delivery of a gene that encodes an enzyme that is able to convert a prodrug into a potent cytotoxin exclusively in target cancer cells. However, it is limited by the lack of suitable enzyme variants and a scarce choice of chemical bonds that could be activated. Therefore, this study is aimed to determine the capability of bacterial amidohydrolases YqfB and D8_RL to activate novel prodrugs and the effect such system has on the viability of eukaryotic cancer cells. We have established cancer cell lines that stably express the bacterial amidohydrolase genes and selected several N.sup.4 -acylated cytidine derivatives as potential prodrugs. A significant decrease in the viability of HCT116 human colon cancer cell lines expressing either the YqfB or the D8_RL was observed after exposure to the novel prodrugs. The data we acquired suggests that bacterial YqfB and D8_RL amidohydrolases, together with the modified cytidine-based prodrugs, may serve as a promising enzyme-prodrug system for gene-directed enzyme prodrug therapy.