Lichen metabolites inhibit UV light and nitric oxide-induced plasmid DNA damage and cell growth in human melanoma cells

In humans both UVA and UVB cause gene mutations and suppress immunity, and these two biological events caused by UV lead to skin cancer. Inhibition of reactive oxygen species (ROS) and reactive nitrogen species (RNS) appears particularly promising as ROS and RNS production by both UVA and UVB contributes to inflammation, immunosuppression, gene mutation and carcinogenesis [1]. Chilean lichens live in regions where the UVR is particularly intensive, and in these conditions, they are stimulated to synthesize metabolites with a strong absorption in the UV region, that exhibit a large variety of biological activity. In a previous study we isolated sphaerophorin, pannarin and epiphorellic acid-1 from Sphaerophorus globosus, different species of the genus Psoroma (Psoroma reticulatum, P. pulchrum, P. palladium) and Cornicularia epiphorella, respectively [2,3]. In this work, we evaluated, in cell free systems, the effect of lichen compounds on pBR322 DNA cleavage induced by nitric oxide and by hydroxyl radicals, generated from UV-photolysis of hydrogen peroxide, and their superoxide anion scavenging capacity. In addition, we investigated the growth inhibitory activity of these natural compounds against a human melanoma cell line (M14). Under our experimental conditions, sphaerophorin, pannarin and epiphorellic acid-1 showed a protective effect on DNA damage and exhibited a superoxide dismutase like effect, but only sphaerophorin and pannarin were able to reduce significantly (p<0.001) the vitality of M14 cells, inducing apoptotic cell death, as demonstrated by the high fragmentation of genomic DNA and by a significant increase (p<0.001) of caspase-3 activity.

References: [1] Russo, P.A.J. and Halliday, G.M. (2006) Photobiol. 155: 408–415. [2] Qhilhot, W. et al. (1989) Ser. Cient. INACH 39: 75–89. [3] Piovano, M. et al. (1989) J. Nat. Prod. 52: 191–192.