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...

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Bibliographic Details
Published in:Cancer letters 2003-03, Vol.191 (2), p.165-170
Main Authors: Shen, Li-Jiuan, Lin, Wen-Chun, Beloussow, Karin, Shen, Wei-Chiang
Format: Article
Language:English
Subjects:
Amino acids
Angiogenesis
Animals
Arginine - metabolism
Arginine deprivation
Argininosuccinate Synthase - metabolism
Argininosuccinate synthetase
Biological and medical sciences
Cancer
Cancer therapies
Cell culture
Cell Division - drug effects
Cell growth
Cell Line
Cell Survival - drug effects
Citrulline - metabolism
Cloning
Cricetinae
Dogs
Drug Resistance
Enzymes
Humans
Hydrolases - isolation & purification
Hydrolases - pharmacology
Medical sciences
Mice
Molecular weight
Mycoplasma - enzymology
Proteins
Recombinant arginine deiminase
Recombinant Proteins
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Summary: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.
ISSN:0304-3835
1872-7980
DOI:10.1016/S030-43835(02)00693-6