In vivo anti-tumor activity of arginine deiminase purified from Mycoplasma arginini

H. Takahu, M. Takase, S-I. Abe, H. Hayashi and K. Miyazaki
International Journal of Cancer (1992), Vol. 51 pages 244-249

Arginine deiminase (EC 3.5.3.6) was purified to homogeneity from the cell extract of Mycoplasma arginini by molecular-sieve anion-exchange and arginine affinity chromatographies. The purified enzyme was composed of 2 identical sub-units with a molecular weight of 45,000 and a pI of 4.7. Its V_max value and K_m value for L-arginine were estimated to be 50 units/mg protein and 0.2 mM, respectively. It exerted maximal enzyme activity at pH 6.0 - 7.5 and 50 °C. The arginine deiminase was stable at neutral pH. When injected i.v. into mice, the half-life of arginine deiminase in blood was about 4 hr. In culture, the enzyme strongly inhibited the growth of 6 kinds of mouse tumor cell lines by depleting L-arginine in the culture media. When the in vivo growth-inhibitory activity of arginine deiminase was tested for the 6 tumor cell lines, i.p. administration of the purified enzyme effectively prolonged the survival time of the mice injected with all kinds of tumor cell lines. Especially, the in vivo growth of a hepatoma cell line, MH134, was completely prevented by the daily administration of at a dose of 0.2 mg/mouse for 14 days. These results raise the possibility of the use of arginine deiminase from Mycoplasma arginini as a new anti-tumor drug.