Chapters authored
Arginine Metabolism: An Enlightening Therapeutic Attribute for Cancer Treatment
Arginine is well known semi-essential amino acid used in protein biosynthesis through several metabolic pathways. It is majorly obtained from nutrients sources and synthesized by the urea cycle in the body using citrulline. Arginine found to be involved in several mechanisms including; hormone synthesis, cell division, activation of the immune system, ammonia disposal and wound healing and also in the production of nitric oxide (NO) and polyamines. During cancer persistence, the biosynthesis of arginine is not sufficient to compensate for their higher nutritional requirements but extracellular availability of arginine is also required. Therefore, the consequences of arginine deprivation may represent a novel targeting therapy to cure cancer. The impact of different arginine deprivation agents and their mechanism of action always found to be correlated with NO and polyamine levels. Arginine deprivation strategy to hamper the proliferation of cancerous cells and their migration is represented as a new approach to cure cancer by inhibiting the argininosuccinate synthetase1 (ASS1) expression and NO and polyamines production. ASS1 is the first key enzyme that converts citrulline to arginine and numerous tumors such as hepatocellular carcinoma, melanoma, mesotheliomas and renal cancer do not express ASS1 and main focused enzyme for cancer treatment. Degradation of arginine by the enzyme arginine deiminase (ADI) specifically triggers the arginine elimination and inhibition of cancer migration. Though, ADI is a microbial enzyme but has a high affinity to arginine and converts arginine into citrulline and NH3. This produced citrulline can be recycled back to arginine in normal cells where ASS1 expression is very high in comparison to ASS1-negative tumor cells. A modified form of ADI with pegylate (ADI-PEG20) has been formulated which showed both in-vivo and in-vitro activity against hepatocellular carcinoma and melanoma by inducing apoptosis. In this chapter, we have majorly discussed arginine production with different pathways and how its degradation into other metabolic active compounds involved in cancer treatment. Moreover, how arginine deprivation is directly taking part in the inhibition of cancer cell proliferation and its migration.
Part of the book: Bioactive Compounds