A Comparative Survey of Anti-Melanoma and Anti-Inflammatory Potential of Usnic Acid Enantiomers-A Comprehensive In Vitro Approach.

Agnieszka Galanty,Joanna Gdula-Argasińska,Karolina Grabowska,Paulina Koczurkiewicz-Adamczyk,Irma Podolak,Paweł Zagrodzki,Dagmara Wróbel-Biedrawa,Elżbieta Pękala,Paweł Paśko

doi:10.3390/ph14090945

Abstract

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.

Highlights

Melanoma is a form of skin cancer characterised by rapid development, poor prognosis, and high mortality
In the first step of the experiment, the impact of usnic acid enantiomers on the viability of HTB140, A375 and WM793 melanoma cells was determined, after standard 24 h and after prolonged 48 h exposure (Table 1). Both compounds significantly affected the viability of the tested cell lines in a dose- and time-dependent manner, but in general (+)usnic acid revealed a stronger cytotoxic effect (p < 0.001) than its left-handed counterpart
The results of our study indicate that both usnic acid enantiomers have anti-hyaluronidase potential, which may be another argument for considering these compounds as anti-melanoma agents

Summary

Introduction

Melanoma is a form of skin cancer characterised by rapid development, poor prognosis, and high mortality. It is the most dangerous type of skin cancer due to its prominent metastasis and resistance to radio- and chemotherapy [1,2]. Much effort has been made worldwide, the effectiveness of anti-melanoma therapy is still not satisfactory. One of the reasons for chemotherapy resistance and treatment failures is the phenotypic heterogeneity of tumour cells. Like inflammation, concomitant with cancer, may affect therapy effectiveness.

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