Název:
Screening Cyanobacteria for Apoptosis Induction in Human Cancer Cell Lines: Discovery of a Novel Compound Nocuolin A
Autoři:
VORÁČOVÁ, Kateřina Typ dokumentu: Disertační práce
Rok:
2017
Jazyk:
cze
Abstrakt: Cancer-related diseases are mostly associated with reduced or inappropriate cell death. This thesis focuses on secondary cyanobacterial metabolites which induce apoptosis in human cancer cells in vitro and thus may serve as potential drug hits. Screening and selection of active natural extracts clearly precede activity-guided isolation of a bioactive compound itself. Summarizing the results of phenotypic screening of cyanobacterial extracts for inducers of apoptosis, I show that adjustment of measurement the activity of key apoptotic enzymes, caspases, per cell significantly enlarges the pool of detected hits. This could be of particular importance, since this correction is relevant for complex natural extracts as well as chemical libraries of pure compounds, and moreover applicable all the way from small-sized screens to high-throughput ones. Further, I investigated the apoptosis inducing activity of nocuolin A (NoA) a new cyanobacterial compound isolated and described by our group. NoA shows remarkable characteristics regarding its structure (1,2,3-oxadiazine heterocycle), biosynthetic origin and also its biological activity. It induces caspase-dependent apoptosis and shows potency against a panel of nine human cancer cell lines, which makes NoA a pharmaceutically interesting compound. I also bring the first insights into elucidation of its mode of action in cancer cells in vitro.
Klíčová slova:
apoptosis; cancer; cyanobacteria; nocuolin; secondary metabolites; apoptosis; cancer; cyanobacteria; nocuolin; secondary metabolites Citace: VORÁČOVÁ, Kateřina. Screening Cyanobacteria for Apoptosis Induction in Human Cancer Cell Lines: Discovery of a Novel Compound Nocuolin A . České Budějovice, 2017. disertační práce (Ph.D.). JIHOČESKÁ UNIVERZITA V ČESKÝCH BUDĚJOVICÍCH. Přírodovědecká fakulta
Instituce: Jihočeská univerzita v Českých Budějovicích
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Plný text je dostupný v digitálním repozitáři JČU. Původní záznam: http://www.jcu.cz/vskp/25035