Ratio-dependent effects of photoactivated hypericin and manumycin A on their genotoxic and mutagenic potential

• Published in: Chemico-biological interactions 2023-04, Vol.374, p.110421-110421, Article 110421
• Main Authors: Zajičková, Terézia, Kyzek, Stanislav, Ďurovcová, Ivana, Ševčovičová, Andrea, Gálová, Eliška
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents; Combined treatment; Comet Assay; DNA Damage; Genotoxicity; Humans; Interactions; Manumycin A; Mutagenicity; Mutagenicity Tests; Mutagens - toxicity; Photoactivated hypericin
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2023.110421

Natural compounds originated from plants and microorganisms and their combinations are currently being investigated as a possible treatment for several diseases including cancer. Hypericin (photodynamically-active pigment from Hypericum perforatum L.) and manumycin A (inhibitor of farnesyltransferase from Streptomyces parvulus) belong to the chemicals potentially applicable in clinical practice. In this study we evaluated potential cytotoxic (via trypan blue exclusion test), genotoxic (via DNA-topology and comet assays), and mutagenic effects (via bacterial reverse mutation test) of these compounds and their combinations considering the molecular mechanism of their action in cell-free and cellular systems. Our results did not reveal neither cytotoxic nor mutagenic activities of tested compounds and their combinations. Regarding the genotoxic potential, no damage of plasmid DNA in cell-free system was detected. On the other hand, photoactivated hypericin and manumycin A were able to induce primary DNA damage in human lymphocytes analyzed by comet assay. The possible antagonistic interactions between these two metabolites were estimated using SynergyFinder software analysis and experimental data obtained from comet assay. Our findings indicate that not only the presence of substances, but also their ratio plays an important role in resulting effects of the combined treatment in cellular system. •Photoactivated hypericin, manumycin A and their combination do not induce plasmid DNA damage in a cell-free system.•DNA damage of human lymphocytes was identified after the treatment with photoativated hypericin and manumycin A.•Mutagenic/cytotoxic effects were not observed in bacterial and eukaryotic cells.•The final effects of metabolites are concentration- and ratio-dependent.