Miyazaki K, Takaku H, Umeda M, Fujita T, Huang W D, Kimura T, Yamashita J, Horio T
Kihara Institute for Biological Research, Yokohama City University, Japan.
Cancer Res. 1990 Aug 1;50(15):4522-7.
Two kinds of growth-inhibitory substances were found in culture of a Rous sarcoma virus-transformed rat liver cell line, RSV-BRL. The two substances were purified from the serum-free culture medium and identified as transforming growth factor beta 1 and Mycoplasma-derived arginine deiminase (EC 3.5.3.6), respectively. The arginine deiminase was an acid-labile but dithiothreitol-resistant protein with a molecular weight of 45,000 and pI 4.7. Its Km value for L-arginine was 0.3 mM, which is about 30 times lower than that of bovine liver arginase. It was stable and active under culture conditions. When added into cultures, the arginine deiminase inhibited the growth of various human cancer cell lines at a dose of 5 ng/ml or higher by depleting L-arginine in the culture media. This effective dose was about 1000 times lower than that of bovine liver arginase. These results suggested the possibility of chemotherapeutic use of arginine deiminase for human cancers.
在劳氏肉瘤病毒转化的大鼠肝癌细胞系RSV-BRL的培养物中发现了两种生长抑制物质。这两种物质从无血清培养基中纯化出来，分别鉴定为转化生长因子β1和支原体来源的精氨酸脱亚氨酶（EC 3.5.3.6）。精氨酸脱亚氨酶是一种对酸不稳定但对二硫苏糖醇有抗性的蛋白质，分子量为45000，pI为4.7。其对L-精氨酸的Km值为0.3 mM，约为牛肝精氨酸酶的30分之一。它在培养条件下稳定且有活性。当添加到培养物中时，精氨酸脱亚氨酶通过消耗培养基中的L-精氨酸，以5 ng/ml或更高的剂量抑制各种人类癌细胞系的生长。该有效剂量比牛肝精氨酸酶低约1000倍。这些结果提示了精氨酸脱亚氨酶用于人类癌症化疗的可能性。
