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

Autor: Barbara Sciandrone, Roméo Arago Dougué Kentsop, Roberta Pensotti, Gianluca Ottolina, Iride Mascheretti, Monica Mattana, Maria Elena Regonesi
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Molecules, Vol 29, Iss 23, p 5516 (2024)
Druh dokumentu: article
ISSN: 1420-3049
DOI: 10.3390/molecules29235516
Popis: 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.
Databáze: Directory of Open Access Journals
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