| Autor: |
Sciandrone B; Department of Biotechnologies and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy., Kentsop RAD; Institute of Agricultural Biology and Biotechnology, National Research Council, 20133 Milan, Italy., Pensotti R; Department of Biotechnologies and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy., Ottolina G; Institute of Chemical Sciences and Technologies 'Giulio Natta', National Research Council, 20131 Milan, Italy., Mascheretti I; Institute of Agricultural Biology and Biotechnology, National Research Council, 20133 Milan, Italy., Mattana M; Institute of Agricultural Biology and Biotechnology, National Research Council, 20133 Milan, Italy., Regonesi ME; Department of Biotechnologies and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy.; Milan Center of Neuroscience (NeuroMI), 20126 Milan, Italy. |
| Abstrakt: |
The screening of plant-derived compounds with anti-cancer properties is a promising strategy to meet the growing need for new, safe and effective anti-cancer drugs. Justicidin B is a plants secondary metabolite that displays anti-cancer properties in several tumor cells. Therefore, it represents a good candidate. We used the 3R-compliant organism Caenorhabditis elegans to evaluate the safety of justicidin B produced by in vitro -grown adventitious roots of Linum lewisii . We showed that a dose of 100 µg/mL justicidin B does not affect worm vitality in either short-term or chronic administration; in contrast, the 200 µg/mL dose induces a lifespan reduction, but only in short-term daily treatment. We attributed this effect to its accumulation in lipofuscin granules in the pharynx as observed through confocal analysis. HPLC analysis confirmed the higher accumulation justicidin B with a 200 µg/mL dose but also revealed the presence of metabolic derivatives that could be responsible for the toxicity. We also demonstrated that the 100 µg/mL dose does not affect worm fertility or development. Our results highlight the safety of justicidin B, supporting its employment in cancer therapy, and encourage the use of a C. elegans model as an appropriate tool to assess compounds' toxicity before moving to more complex organisms. |
