Biochemical Characterization of a Kunitz-Type Protease Inhibitor From Mimosa regnellii and Its Effects on Melanoma Cell Viability and Angiogenesis.

Cancer is a term used to represent more than 100 diseases, including malignant tumors of different localizations. Among these types, cutaneous melanoma is one of the most common types of skin cancer worldwide. Newer, non-invasive, and more effective forms of treatment are urgently needed. Recently, the cancer membrane has emerged as a novel target for new anticancer drugs. Serine protease inhibitors are researched across all kingdoms; however, the Plantae kingdom is a more sustainable producer of bioactive molecules, including serine protease inhibitors. In this study, a Kunitz trypsin inhibitor (JTI) purified by RP-HPLC from Mimosa regnellii seeds was sequenced, its inhibitory activity quantified, and its inhibition constant determined. It was then tested for its ability to induce cell death via the apoptotic pathway in B16-F10 mouse melanoma cells. To evaluate its pro-apoptotic capacity, the inhibitor's effects on reactive oxygen species release, calcium release, cell morphological changes, and the inhibition of angiogenic and migratory activities of rabbit endothelial cells (RaEC) were also assessed in vitro. Tests for toxicity against normal cells were performed, confirming that JTI acts on melanoma cells with an IC50 of 0.65 µM. These results suggest that JTI has potential for use in melanoma treatment.