Sciandrone Barbara, Kentsop Roméo Arago Dougué, Pensotti Roberta, Ottolina Gianluca, Mascheretti Iride, Mattana Monica, Regonesi Maria Elena
Department of Biotechnologies and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy.
Institute of Agricultural Biology and Biotechnology, National Research Council, 20133 Milan, Italy.
Molecules. 2024 Nov 22;29(23):5516. doi: 10.3390/molecules29235516.
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 to evaluate the safety of justicidin B produced by -grown adventitious roots of . 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 model as an appropriate tool to assess compounds' toxicity before moving to more complex organisms.
筛选具有抗癌特性的植物源化合物是满足对新型、安全且有效的抗癌药物日益增长需求的一种有前景的策略。异紫堇定B是一种植物次生代谢产物，在多种肿瘤细胞中表现出抗癌特性。因此，它是一个很好的候选物。我们使用符合3R原则的生物来评估由生长的不定根产生的异紫堇定B的安全性。我们发现，100µg/mL剂量的异紫堇定B在短期或长期给药中均不影响线虫活力；相比之下，200µg/mL剂量仅在短期每日处理中会导致寿命缩短。通过共聚焦分析观察到，我们将这种效应归因于其在咽部脂褐素颗粒中的积累。高效液相色谱分析证实，200µg/mL剂量的异紫堇定B积累量更高，但也揭示了可能导致毒性的代谢衍生物的存在。我们还证明，100µg/mL剂量不影响线虫的繁殖力或发育。我们的结果突出了异紫堇定B的安全性，支持其在癌症治疗中的应用，并鼓励在转向更复杂的生物体之前，使用模型作为评估化合物毒性的合适工具。
