In Vitro Anti-melanoma Efficacy and Selectivity of Withania somnifera

Withania somnifera (L.) Dunal, Solanaceae, is a shrub known to have anti-cancer, anti-hypertensive, anti-inflammatory, and immunostimulatory properties. The main bioactive compounds present in this plant are steroidal lactones or withanolides. The anti-melanoma efficacy of W. somnifera extracts and bioactive compounds and any selectivity for melanoma A375 cells versus keratinocytes HaCaT was investigated. Withaferin A and withanolide A were selected as marker compounds. Three crude extracts were prepared using water, and 80% and 50% ethanol as solvents. Cytotoxicity and apoptosis assays were carried out on A375 and HaCaT cells to determine the effects of the marker compounds and crude W. somnifera extracts. Further investigations were carried out to determine the influence of crude extract encapsulation in solid lipid nanoparticles and the presence of an extracellular matrix (Matrigel). Both withaferin A and withanolide A presented with cytotoxic and apoptotic properties that were relatively selective for A375 cells, as indicated by the IC 50 values of withaferin A (26.25 μg/ml), withanolide A (80.61 μg/ml), and their combination (13.87 μg/ml). Results obtained revealed that the pure compounds were selective for melanoma cells and more active than the crude extracts in both 2D and 3D environments. Graphical abstract