Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, Ukraine.
Cell Biol Int. 2010 Nov;34(11):1085-9. doi: 10.1042/CBI20100451.
Single amino acid Arg (arginine) deprivation is currently considered as a therapeutic approach to treat certain types of tumours; the molecular mechanisms that underlie tumour cell sensitivity or resistance to Arg restriction are still little understood. Here, we address the question of whether endogenous levels of key Arg metabolic enzymes [catabolic: arginases, ARG1 (arginase type 1) and ARG2 (arginase type 2), and anabolic: OTC (ornithine transcarbamylase) and ASS (argininosuccinate synthetase)] affect cellular responses to arginine deprivation in vitro. Human epithelial cancer cells of different organs of origin exhibiting variable sensitivity to Arg deprivation provided the experimental models. Neither the basal expression status of the analysed enzymes, nor their changes upon arginine withdrawal correlated with cancer cell sensitivity to arginine deprivation. However, the ability to utilize exogenous Arg precursors (ornithine and citrulline) for growth in Arg-deficient medium strongly correlated with expression of the corresponding enzymes, OTC and ASS. We also observed that OTC expression was below the level of detection in all the types of tumour cells analysed, suggesting that in vitro, at least for them, Arg is an essential amino acid.
目前，单一氨基酸精氨酸（Arg）缺乏被认为是治疗某些类型肿瘤的一种治疗方法；但肿瘤细胞对 Arg 限制的敏感性或抗性的分子机制仍知之甚少。在这里，我们探讨了关键 Arg 代谢酶[分解代谢：精氨酸酶（ARG1 和 ARG2）和鸟氨酸转氨甲酰酶（OTC），合成代谢：精氨琥珀酸合成酶（ASS）]的内源性水平是否会影响体外细胞对 Arg 缺乏的反应这一问题。不同起源器官的人上皮癌细胞对 Arg 缺乏的敏感性不同，为实验模型。分析的酶的基础表达状态，以及它们在精氨酸缺失时的变化，与癌细胞对精氨酸缺乏的敏感性都没有相关性。然而，利用外源性 Arg 前体（鸟氨酸和瓜氨酸）在缺乏 Arg 的培养基中生长的能力与相应酶（OTC 和 ASS）的表达强烈相关。我们还观察到，在所有分析的肿瘤细胞类型中，OTC 的表达都低于检测水平，这表明在体外，至少对这些细胞来说，Arg 是一种必需氨基酸。
