title: Cytotoxicity evaluation of large cyanobacterial strain set using selected human and murine in vitro cell models.
abstract: The production of cytotoxic molecules interfering with mammalian cells is extensively reported in cyanobacteria. These compounds may have a use in pharmacological applications; however, their potential toxicity needs to be considered. We performed cytotoxicity tests of crude cyanobacterial extracts in six cell models in order to address the frequency of cyanobacterial cytotoxicity to human cells and the level of specificity to a particular cell line. A set of more than 100 cyanobacterial crude extracts isolated from soil habitats (mainly genera Nostoc and Tolypothrix) was tested by MTT test for in vitro toxicity on the hepatic and non-hepatic human cell lines HepG2 and HeLa, and three cell systems of rodent origin: Yac-1, Sp-2 and Balb/c 3T3 fibroblasts. Furthermore, a subset of the extracts was assessed for cytotoxicity against primary cultures of human hepatocytes as a model for evaluating potential hepatotoxicity. Roughly one third of cyanobacterial extracts caused cytotoxic effects (i.e. viability<75%) on human cell lines. Despite the sensitivity differences, high correlation coefficients among the inhibition values were obtained for particular cell systems. This suggests a prevailing general cytotoxic effect of extracts and their constituents. The non-transformed immortalized fibroblasts (Balb/c 3T3) and hepatic cancer line HepG2 exhibited good correlations with primary cultures of human hepatocytes. The presence of cytotoxic fractions in strongly cytotoxic extracts was confirmed by an activity-guided HPLC fractionation, and it was demonstrated that cyanobacterial cytotoxicity is caused by a mixture of components with similar hydrophobic/hydrophilic properties. The data presented here could be used in further research into in vitro testing based on human models for the toxicological monitoring of complex cyanobacterial samples.
authors.affiliation: Institute of Microbiology, Centre Algatech, Czech Academy of Sciences, Opatovický mlýn, 379 81 Třeboň, Czech Republic. Electronic address: hrouzekp@gmail.com.
authors.forename: Pavel
authors.initials: P
authors.lastname: Hrouzek
authors.affiliation: Institute of Microbiology, Centre Algatech, Czech Academy of Sciences, Opatovický mlýn, 379 81 Třeboň, Czech Republic.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kapuścik
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University in Olomouc, Hněvotínská 3, 775 15 Olomouc, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Vacek
authors.affiliation: Institute of Microbiology, Centre Algatech, Czech Academy of Sciences, Opatovický mlýn, 379 81 Třeboň, Czech Republic; University of South Bohemia, Faculty of Sciences, Department of Molecular and Cell Biology, Branišovská 31, České Budějovice, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Voráčová
authors.affiliation: Institute of Microbiology, Centre Algatech, Czech Academy of Sciences, Opatovický mlýn, 379 81 Třeboň, Czech Republic.
authors.forename: Jindřiška
authors.initials: J
authors.lastname: Paichlová
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University in Olomouc, Hněvotínská 3, 775 15 Olomouc, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Kosina
authors.affiliation: Saint-Petersburg State University, Oranienbaumskoye shosse 2, 198504 St. Petersburg, Russia.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Voloshko
authors.affiliation: Institute of Ecosystem Study, CNR, via Madonna del Piano 10, 50019 Sesto Fiorentino, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ventura
authors.affiliation: Institute of Microbiology, Centre Algatech, Czech Academy of Sciences, Opatovický mlýn, 379 81 Třeboň, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Kopecký
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D002460:Cell Line; D045424:Complex Mixtures / Q000633:toxicity*; D000458:Cyanobacteria / Q000737:chemistry*; D003603:Cytotoxins / Q000032:analysis*; D005347:Fibroblasts; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D045424:Complex Mixtures; D003603:Cytotoxins; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue
keywords: Cell lines; Cyanobacteria; Cytotoxicity; Hepatocytes; MTT test; Primary cultures