Szende Bela, Tyihák Erno, Trézl Lajos
Department of Pathology and Experimental Cancer Research, Semmelweis University and Molecular Pathology Research Group, Hungarian Academy of Sciences, Budapest, H-1085.
Cancer Cell Int. 2001 Dec 17;1(1):3. doi: 10.1186/1475-2867-1-3.
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.
补充和剥夺L-精氨酸均会影响细胞增殖。高剂量L-精氨酸对肿瘤的作用取决于其光学构型：L-精氨酸具有刺激作用，而D-精氨酸具有抑制作用。富含精氨酸的六肽可抑制肿瘤生长。从细胞培养物中去除L-精氨酸可增强细胞凋亡。一氧化氮合酶抑制剂（如NG-单甲基-L-精氨酸）的促凋亡作用是通过抑制精氨酸酶途径来体现的。NG-羟甲基-L-精氨酸可导致细胞培养物中的细胞凋亡，并抑制多种可移植小鼠肿瘤的生长。这些不同的生物学活性是通过甲醛（HCHO）表现出来的，因为游离和结合形式的L-精氨酸的胍基可与内源性HCHO迅速反应，形成NG-羟甲基化衍生物。L-精氨酸是生物系统中的甲醛捕获、转运和供体分子。NG-甲基化和羟甲基化精氨酸代谢过程中产生的甲醛在细胞增殖和死亡中的作用得以显现。推测具有抗凋亡作用的纯合子Arg 72-p53基因型可能会增加某些癌症的易感性。L-精氨酸及其甲基化衍生物的多种生物学效应需要对其在化学预防和癌症治疗中的可能应用进行进一步的深入研究。
