Galanty Agnieszka, Zagrodzki Paweł, Gdula-Argasińska Joanna, Grabowska Karolina, Koczurkiewicz-Adamczyk Paulina, Wróbel-Biedrawa Dagmara, Podolak Irma, Pękala Elżbieta, Paśko Paweł
Department of Pharmacognosy, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
Department of Food Chemistry and Nutrition, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
Pharmaceuticals (Basel). 2021 Sep 21;14(9):945. doi: 10.3390/ph14090945.
Usnic acid (UA) is a chiral lichen metabolite with an interesting pharmacological profile. The aim of this study was to compare the anti-melanoma effect of (+)-UA and (-)-UA in an in vitro model by studying their impact on the cells as well as the processes associated with cancer progression. The effect of UA enantiomers on the viability, proliferation, and invasive potential of three melanoma cell lines (HTB140, A375, WM793) was evaluated. Their interaction with a chemotherapeutic drug-doxorubicin was assessed by isobolographic analysis. Anti-inflammatory and anti-tyrosinase properties of (+)-UA and (-)-UA were also examined. Both UA enantiomers dose- and time-dependently decreased the viability of all three melanoma cell lines. Their synergistic effect with doxorubicin was observed on A375 cells. (+)-Usnic acid at a sub-cytotoxic dose strongly inhibited melanoma cells migration. Both UA enantiomers decreased the release of pro-inflammatory mediators. The cytotoxic effect of (+)-UA and (-)-UA depends greatly on the melanoma cell type; however, the overall anti-melanoma potential is perspective. Our results indicate that the strategy of combining usnic acid enantiomers with cytostatic drugs may be an interesting option to consider in combating melanoma; however, further studies are required.
松萝酸(UA)是一种具有有趣药理学特性的手性地衣代谢产物。本研究的目的是通过研究(+)-UA和(-)-UA对细胞以及与癌症进展相关过程的影响,在体外模型中比较它们的抗黑色素瘤作用。评估了UA对映体对三种黑色素瘤细胞系(HTB140、A375、WM793)的活力、增殖和侵袭潜能的影响。通过等效应线图分析评估了它们与化疗药物阿霉素的相互作用。还检测了(+)-UA和(-)-UA的抗炎和抗酪氨酸酶特性。两种UA对映体均呈剂量和时间依赖性地降低了所有三种黑色素瘤细胞系的活力。在A375细胞上观察到它们与阿霉素的协同作用。亚细胞毒性剂量的(+)-松萝酸强烈抑制黑色素瘤细胞迁移。两种UA对映体均降低了促炎介质的释放。(+)-UA和(-)-UA的细胞毒性作用在很大程度上取决于黑色素瘤细胞类型;然而,总体抗黑色素瘤潜力是有前景的。我们的结果表明,将松萝酸对映体与细胞抑制药物联合使用的策略可能是对抗黑色素瘤时值得考虑的一个有趣选择;然而,还需要进一步的研究。