Inhibitors of proteases as anticancer drugs
Abstract:
Proteolytic processes are necessary for normal physiological functions in the body. Failure in the biological control mechanisms of proteolytic activities may cause various diseases, for example, it may enable tumor invasion and metastasis. In the metastatic process, proteolytic enzymes play an important role in mediating passage of the malignant cell through the cell membrane. Tumor cell migration and invasion into the surrounding extracellular matrix is facilitated by a variety of cell surface-associated proteolytic enzymes: matrix metalloproteinases (MMPs), cysteine proteases including cathepsins B and L, aspartic protease cathepsin D, and serine proteases including plasmin and urokinase plasminogen activator (uPA). Many of the natural and synthetic inhibitors of the proteases prevent the dissemination of cancer cells and have also inhibitory effect on tumor growth. Thus inhibition of protease activity by low molecular weight inhibitors represents a promising strategy for anticancer and antimetastatic therapy. The review surveys low molecular inhibitors of MMPs, uPA and lysosomal proteases.