Arginine deprivation: a potential therapeutic for cancer cell metastasis? A review

Abstract

Arginine is a semi essential amino acid that is used in protein biosynthesis. It can be obtained from daily food intake or synthesized in the body through the urea cycle using l-citrulline as a substrate. Arginine has a versatile role in the body because it helps in cell division, wound healing, ammonia disposal, immune system, and hormone biosynthesis. It is noteworthy that l-arginine is the precursor for the biosynthesis of nitric oxide (NO) and polyamines. In the case of cancer cells, arginine de novo synthesis is not enough to compensate for their high nutritional needs, forcing them to rely on extracellular supply of arginine. In this review, we will go through the importance of arginine deprivation as a novel targeting therapy by discussing the different arginine deprivation agents and their mechanism of action. We will also focus on the factors that affect cell migration and on the influence of arginine on metastases through polyamine and NO.

Obesity and Cancer Metastasis: Molecular and Translational Perspectives

“…Citrulline is secreted into the ECM and is taken up by stromal adipocytes, before being converted back into arginine and released for cancer cells [ 146 ]. Depriving tumor cells of arginine has cytotoxic effects through apoptosis or autophagy depending upon the tumor type, and decreasing the ability of tumor cells to migrate and adhere to the ECM [ 147 ]. Arginine dependent migration requires arginine to be metabolized by two major enzymes, arginase (ARG1) and nitric oxide synthase (NOS) [ 147 ].…”

“…Depriving tumor cells of arginine has cytotoxic effects through apoptosis or autophagy depending upon the tumor type, and decreasing the ability of tumor cells to migrate and adhere to the ECM [ 147 ]. Arginine dependent migration requires arginine to be metabolized by two major enzymes, arginase (ARG1) and nitric oxide synthase (NOS) [ 147 ]. In HCC, higher expression of ARG1 is positively correlated to aggressive tumor growth and poor disease free survival [ 148 ].…”

Antitumoral Properties of the Nutritional Supplement Ocoxin Oral Solution: A Comprehensive Review

“…Arginine plays an important role in regular cellular functions. In fact, the presence of arginine is needed by tumoral cells for growth, and that circumstance has promoted the concept of using diets in which arginine deprivation could be beneficial for patients [48]. However, arginine has also been reported to represent a critical component of body systems for keeping in check abnormal cells such as tumor ones [49].…”

Effect of S-ademethionine on Arginine Content and Its Metabolites in Patients with Chronic Lymphocytic Leukemia During Chemotherapy

“…В умовах пухлинного процесу фіксують нестачу аргініну, що пов'язано із надмірним поглинанням останнього клітинами пухлини. Доведено, що клітини пухлини є аргінін-ауксотрофними, тобто такими, що втратили можливість підтримувати власний рівень аргініну за рахунок його ресинтезу [6,14,15]. Даний факт обумовлений відсутністю на пухлинних клітинах експресії аргінінсукцинатсинтази і аргінінсукцинатліази, які метаболізують цитрулін до аргініну.…”