Proteases as Targets in Anticancer Therapy Using Their Inhibitors

Proteases, also known as proteolytic enzymes, are enzymes that catalyze the breakdown of proteins by hydrolysis of peptide bonds. Earlier proteases were considered as only protein degrading enzymes, however now dramatically the view has changed. Proteases are extremely important signalling molecules that are involved in numerous vital processes like apoptosis, cell growth and activation, adhesion, invasion, cell migration and metastasis, protein secretion, cellular interactions and signal transduction, phagocytosis and angiogenesis. Thus, show complete anticancer mechanism. And proteases from all six classes have been found to be involved in tumor growth and progression. Inhibitors of such proteases are emerging with promising therapeutic uses in the treatment of cancer. Protease inhibitor suppression of carcinogenesis is related to ability to effect the expression of certain oncogens and the levels of certain types of proteolytic activities. Protease inhibitors being found to be as special agents in anticancer therapy have been isolated from plants, bacteria and prepared synthetically. Under the same trend different protease inhibitors have been used and are being in clinical and pre-clinical stage. Thus, studying PIs as anticancer agents open a new field for treatment of cancer. Address for correspondence: Dr. Shajrul Amin, Department of Biochemistry, University of Kashmir, Srinagar, 190006, Jammu and Kashmir, India Telephone: +91-9419018174. E-mail: [email protected] INTRODUCTION From the literature available it is clear that all five major classes of proteases are involved in tumor growth and progression. Protease enzymes selectively catalyzing the hydrolysis of polypeptide bond are crucial for disease propagation and inhibitors of such proteases are emerging with promising therapeutic uses in the treatment of diseases like cancers. Inhibitors of these proteases can suppress several stages of carcinogenesis including initiation, promotion and progression although their mechanism of action is not yet fully clear. Studies have suggested that the protease inhibitors which prevent carcinogenesis affect processes in the early stages of carcinogenesis although they can be effective at long times period after carcinogen exposure in both in vitro and in vivo systems, while there is a strong evidence that these protease inhibitors can affect both the initiation and promotion stages of carcinogenesis and they have no effect on already transformed cells. Results have suggested that the first event in carcinogenesis is a high frequency epigenetic event and that a later event, presumably genetic, leads to the malignant state. Effect of protease inhibitors on the following phenomenon are thought to be related to their anti carcinogenic activity: 1) Ability to effect the expression of certain oncogenes, 2) Ability to return carcinogen increased levels of certain proteolytic activities for example, Boc-valproargMca hydrolyzing activity to normal levels (Kennedy 1993). Clawson, 1996 categorized the effects of Protease Inhibitors into three basic groups: a) Signal transduction pathways b) DNA repair processes c) Nuclear proteases From the studies it is simply clear that protease inhibitors can be used as drugs to treat the various tumor patients. Under the same studies different protease inhibitors have been used in clinical and pre-clinical stage. Many new ECP (Extra Cellular Proteases) inhibitors are currently under clinical investigation and a significant increase in new therapies based on protease inhibition can be expected in the coming years. Protease Inhibitors and Antitumorigenesis PI (Protease inhibitor) represent an important role in regulation of various cellular physiological and biological processes, including cell cycle, cell death, differentiation and the immune response (Fan et al. 2001; Buhling et al. 2006). Previous studies have shown the anticancer effect and probable mechanisms of the natural and chemical PI in vitro. © Kamla-Raj 2013 J Life Sci, 5(2): 133-138 (2013)