Review

Role of arginine and its methylated derivatives in cancer biology and treatment

Bela Szende¹ , Erno Tyihák² and Lajos Trézl³

¹  Department of Pathology and Experimental Cancer Research, Semmelweis University and Molecular Pathology Research Group, Hungarian Academy of Sciences, Budapest, H-1085

²  Plant Protection Institute, Hungarian Academy of Sciences, Budapest, H-1022

³  Department of Organic Chemistry, Budapest University of Technology and Economics, Budapest, H-1111, Hungary

author email corresponding author email

Cancer Cell International 2001, 1:3doi:10.1186/1475-2867-1-3

Published:	17 December 2001

Abstract

Both L-arginine supplementation and deprivation influence cell proliferation. The effect of high doses on tumours is determined by the optical configuration: L-arginine is stimulatory, D-arginine inhibitory. Arginine-rich hexapeptides inhibited tumour growth. Deprivation of L-arginine from cell cultures enhanced apoptosis. The pro-apoptotic action of NO synthase inhibitors, like NG-monomethyl-L-arginine, is manifested through inhibition of the arginase pathway. NG-hydroxymethyl-L-arginines caused apoptosis in cell cultures and inhibited the growth of various transplantable mouse tumours. These diverse biological activities become manifest through formaldehyde (HCHO) because guanidine group of L-arginine in free and bound form can react rapidly with endogenous HCHO, forming NG-hydroxymethylated derivatives. L-arginine is a HCHO capturer, carrier and donor molecule in biological systems. The role of formaldehyde generated during metabolism of NG-methylated and hydroxymethylated arginines in cell proliferation and death can be shown. The supposedly anti-apoptotic homozygous Arg 72-p53 genotype may increase susceptibility of some cancers. The diverse biological effects of L-arginine and its methylated derivatives call for further careful studies on their possible application in chemoprevention and cancer therapy.