Toxicological Analysis of the Arylnaphthalene Lignan Justicidin B Using a Caenorhabditis elegans Model.

Autor: Sciandrone, Barbara, Kentsop, Roméo Arago Dougué, Pensotti, Roberta, Ottolina, Gianluca, Mascheretti, Iride, Mattana, Monica, Regonesi, Maria Elena
Zdroj: Molecules; Dec2024, Vol. 29 Issue 23, p5516, 17p
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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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