pSK - A Novel Amphibian Skin Bowman-Birk-like Trypsin and TMPRSS2 Inhibitor

摘要

For centuries, extracts of amphibian skin has been widely used as folk medicines. Amphibian skin is a morphologically, biochemically and physiologically multifunctional organ which subserves general survival roles, such as anti-predator, anti-microbial and anti-fungal defense [1,2]. The complex cocktails of bioactive molecules which constitute defensive secretion in the highly-specialized dermal granular glands contain proteins, biogenic amines, alkaloids and a plethora of bioactive peptides. Serine proteases are one of the most well studied grouping of proteins and are involved in key regulatory processes such as peptide hormone precursor processing and release, blood coagulation and complement fixation, and additionally, for their intimate involvement in the pathogenesis of numerous diseases, including cancer, pulmonary emphysema and inflammation [3,4]. TMPRSS2, a type II transmembrane-bound serine protease, has gained interest due to its highly localized expression in the prostate and its overexpression in neoplastic prostate epithelium [5]. Once activated, the serine protease domain of TMPRSS2 is released from the cell surface into the extracellular space. TMPRSS may contribute to the prostate tumor metastasis via the activation of PAR (protease-activated receptor)-2 which belongs to a family of G-protein coupled receptors (PAR-1-4) activated by specific serine proteases expressed in many normal and malignant cell types.