Regulation of angiogenesis and inflammatory pathways by glycyrrhizic acid

Skin cancer accounts for most malignancies across the globe. They are primarily divided into melanoma and nonmelanoma skin malignancies. Nonmelanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma. Glycyrrhetinic acid (GA) is a bioactive compound extracted from licorice that exhibits an inhibition effect on various cancers. GA has been reported to have in vitro cytotoxic effects on several human cancer cells. However, reports on the mode of action and detailed mechanism of GA in vitro in skin cancer disease are limited. Hence, GA’s effect on the human skin cell line BJ and MCC13 was investigated. MTT assay showed that GA had cytotoxic effects on MCC13 cells but was non-toxic to the normal cells of BJ in a time-dose dependent manner. GA also inhibited the angiogenic sprouting of new blood vessels in tumor progression. In gene expression assay, GA induces mitochondrial apoptosis through the induction and inhibition of Cytochrome C and Bcl2 respectively. In conclusion, GA is a potent candidate to induce apoptosis and concurrently inhibit the invasion, migration, and angiogenesis of the MCC13 cell line through increasing TNF-alpha concentration resulting in the necroptotic pathway induction.