Biological Activity and Stability of Aeruginosamides from Cyanobacteria
Marta Cegłowska,
Patrycja Kwiecień,
Karolina Szubert,
Paweł Brzuzan,
Maciej Florczyk,
Christine Edwards,
Alicja Kosakowska,
Hanna Mazur-Marzec
Affiliations
Marta Cegłowska
Institute of Oceanology, Polish Academy of Sciences, Powstańców Warszawy 55, PL-81712 Sopot, Poland
Patrycja Kwiecień
Institute of Oceanology, Polish Academy of Sciences, Powstańców Warszawy 55, PL-81712 Sopot, Poland
Karolina Szubert
Division of Marine Biotechnology, Institute of Oceanography, University of Gdańsk, M. J. Piłsudskiego 46, PL-81378 Gdynia, Poland
Paweł Brzuzan
Department of Environmental Biotechnology, Faculty of Geoengineering, University of Warmia and Mazury in Olsztyn, Słoneczna 45G, PL-10709 Olsztyn, Poland
Maciej Florczyk
Department of Environmental Biotechnology, Faculty of Geoengineering, University of Warmia and Mazury in Olsztyn, Słoneczna 45G, PL-10709 Olsztyn, Poland
Christine Edwards
School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen AB10 7GJ, UK
Alicja Kosakowska
Institute of Oceanology, Polish Academy of Sciences, Powstańców Warszawy 55, PL-81712 Sopot, Poland
Hanna Mazur-Marzec
Division of Marine Biotechnology, Institute of Oceanography, University of Gdańsk, M. J. Piłsudskiego 46, PL-81378 Gdynia, Poland
Aeruginosamides (AEGs) are classified as cyanobactins, ribosomally synthesized peptides with post-translational modifications. They have been identified in cyanobacteria of genera Microcystis, Oscillatoria, and Limnoraphis. In this work, the new data on the in vitro activities of three AEG variants, AEG A, AEG625 and AEG657, and their interactions with metabolic enzymes are reported. Two aeruginosamides, AEG625 and AEG657, decreased the viability of human breast cancer cell line T47D, but neither of the peptides was active against human liver cancer cell line Huh7. AEGs also did not change the expression of MIR92b-3p, but for AEG625, the induction of oxidative stress was observed. In the presence of a liver S9 fraction containing microsomal and cytosolic enzymes, AEG625 and AEG657 showed high stability. In the same assays, quick removal of AEG A was recorded. The peptides had mild activity against three cytochrome P450 enzymes, CYP2C9, CYP2D6 and CYP3A4, but only at the highest concentration used in the study (60 µM). The properties of AEGs, i.e., cytotoxic activity and in vitro interactions with important metabolic enzymes, form a good basis for further studies on their pharmacological potential.
