Optimization of cytotoxic activity of Nocardia sp culture broths using a design of experiments

Autoři: Alba Noël aff001;  Gwendoline Van Soen aff001;  Isabelle Rouaud aff001;  Eric Hitti aff002;  Sophie Tomasi aff001
Působiště autorů: Univ Rennes, CNRS, ISCR–UMR 6226, Rennes, France aff001;  LTSI, UMR_S 1099, UFR Sciences Pharmaceutiques et Biologiques, Rennes, France aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227816


In the context of research for new cytotoxic compounds, obtaining bioactive molecules from renewable sources remain a big challenge. Microorganisms and more specifically Actinobacteria from original sources are well known for their biotechnological potential and are hotspots for the discovery of new bioactive compounds. The strain DP94 studied here had shown an interesting cytotoxic activity of its culture broth (HaCaT: IC50 = 8.0 ± 1.5 μg/mL; B16: IC50 = 4.6 ± 1.8 μg/mL), which could not been explained by the compounds isolated in a previous work. The increase of the cytotoxic activity of extracts was investigated, based on a Taguchi L9 orthogonal array design, after DP94 culture in TY medium using two different vessels (bioreactor or Erlenmeyer flasks). Various culture parameters such as temperature, pH and inoculum ratio (%) were studied. For experiments conducted in a bioreactor, stirring speed was included as an additional parameter. Significant differences in the cytotoxic activities of different extracts on B16 melanoma cancer cell lines, highlighted the influence of culture temperature on the production of cytotoxic compound(s) using a bioreactor. A culture in Erlenmeyer flasks was also performed and afforded an increase of the production of the active compounds. The best conditions for the highest cytotoxicity (IC50 on B16: 6 ± 0.5 μg/mL) and the highest yield (202.0 mg/L) were identified as: pH 6, temperature 37°C and 5% inoculum.

Klíčová slova:

Analysis of variance – Bacterial growth – Cytotoxicity – Experimental design – High performance liquid chromatography – Lichenology – B16 cells – Nocardia


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