Cachrys libanotis L. Extracts: Photocytotoxic Effects on UVA-Irradiated Human Melanoma Cells

Abstract

Melanoma is the most aggressive form of skin cancer. Photochemotherapy, combining the action of a light source and a chemical photosensitizer, is one of the most interesting current therapeutic approaches. Plants represent a rich source of photoactive compounds, and furanocoumarins are some of the most important naturally occurring phytoconstituents. The aim of this study was to evaluate the photocytotoxic potential of Cachrys libanotis L. (Apiaceae) from Southern Italy. This species belongs to a genus rich in furanocoumarins and widely distributed in Europe. The aerial parts of the plant were extracted through both traditional maceration and pressurized cyclic solid-liquid (PCSL) extraction using a Naviglio extractor®. Qualitative and quantitative analyses were performed to detect the coumarin content using GC-MS, and the photocytotoxic effects of the extracts were assessed on UVA-irradiated C32 melanoma cells. The apoptotic responses were also evaluated. Furthermore, the phenolic content and in vitro antioxidant potential were estimated. Xanthotoxin, bergapten and isopimpinellin were identified and quantified. Both extracts affected the cell viability in a concentration-dependent manner after irradiation for 1 h at a dose of 1.08 J/cm2. The sample obtained through PCSL extraction was the most effective, with an IC50 equal to 3.16 μg/mL, a very interesting value if compared with the positive control bergapten. This extract induced upregulation of apoptotic signals such as BAX and PARP cleavage, and in the presence of UVA radiation, it caused a greater upregulation of the p21 protein. The obtained results suggest that the investigated species could be a good candidate for further studies aiming to find new drugs with photocytotoxic potential.