Resistance to the anti-proliferative activity of recombinant arginine deiminase in cell culture correlates with the endogenous enzyme, argininosuccinate synthetase.
Recombinant mycoplasma enzyme, arginine deiminase (rADI), has been proposed as a possible cancer treatment via arginine depletion. However, many cell lines are resistant to rADI-treatment, even though most require arginine for proliferation. We compared eight different cell lines for sensitivity in cell proliferation to the effect of either rADI or arginine deprivation. The activity of argininosuccinate synthetase (AS), the rate-limiting enzyme for converting citrulline to arginine, was also measured. Our results indicate that resistance to rADI-treatment may correlate with cellular AS activity, either constitutive or inducible, allowing cell survival by conversion of the product of the rADI reaction, i.e. citrulline to arginine.
Shen
Li-Jiuan
LJ
Department of Pharmaceutical Sciences, University of Southern California School of Pharmacy, PSC 404B, 1985 Zonal Avenue, Los Angeles, CA 90089-9121, USA.
Lin
Wen-Chun
WC
Beloussow
Karin
K
Shen
Wei-Chiang
WC
D000818:Animals; D001120:Arginine / Q000378:metabolism; D001124:Argininosuccinate Synthase / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002956:Citrulline / Q000378:metabolism; D006224:Cricetinae; D004285:Dogs; D004351:Drug Resistance; D006801:Humans; D006867:Hydrolases / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D009174:Mycoplasma / Q000201:enzymology; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D002956:Citrulline; D001120:Arginine; D006867:Hydrolases; C019723:arginine deiminase; D001124:Argininosuccinate Synthase