The determination of the therapeutic effect of lobaric acid as an innovative strategy in melanoma cancer treatment

Melanoma (skin cancer) is one of the most dangerous and common types of cancer in humans. Melanoma is most found on skin surfaces that are sensitive to the sun (UV) radiation. Due to the side effects of the drugs used in the routine treatment of melanoma, there is a need to identify drug candidate molecules with lower toxicity and side effects and stronger anti-cancer activity. Studies have shown that natural compounds obtained from biological organisms such as plants, fungi, and lichens have anti-cancer drug potential. It has been determined that lobaric acid, a secondary metabolite isolated from species belonging to the Stereocaulon lichen genus, has an important anti-cancer effect on different cancer cells. In this study, the therapeutic effect of lobaric acid on melanoma cancer cells was investigated in vitro. The anti-proliferative effect of lobaric acid on human melanoma cell lines (A-375, MDA-MB 435, G-361, and WM-115) and normal human epidermal melanocyte cells was determined using the MTT and xCELLigence real-time cell analysis system. Cell cycle and apoptosis profile were analyzed using flow cytometry. qRT-PCR was used to evaluate the gene expression level of apoptosis-related genes at the mRNA level, and the apoptotic effect at the protein level was determined by western blot. Our results showed that lobaric acid exerted a dose and time-dependent anti-proliferative effect on the A-375 melanoma cell and induces cell cycle arrest at G0/G1 phase. The gene expression levels of 88 different apoptosis-related genes in the primary apoptosis library panel were studied by qRT-PCR analysis, but results were obtained from 70 target genes, and the expression levels of 54 genes were increased while 16 genes decreased. In addition, it was determined that the level of apoptosis-related proteins (Casp3, Casp7, Casp9, and PARP) were increased. Our obtained result indicated that lobaric acid induces apoptosis through extrinsic pathway by increasing the expression level of the Caspases and PARP. The findings of this study provided a strong basis for the use of lobaric acid as a potential therapeutic agent in the treatment of melanoma. Keywords: Melanoma; Lobaric acid; Apoptosis