Pancreatic cancer cell lines deficient in argininosuccinate synthetase are sensitive to arginine deprivation by arginine deiminase

• DOI: 10.1002/ijc.23723
• Publication Date: 2008-07-25T18:54:23Z
• Authors: Tawnya L. Bowles; Randie Kim; Joseph Galante; Colin M. Parsons; Subbulakshmi Viru...; Hsing‐Jien Kung; Richard J. Bold
• Keywords: Arginine deiminase; Argininosuccinate synthase; Argininosuccinate lyase

Abstract Eukaryotic cells can synthesize the non‐essential amino acid arginine from aspartate and citrulline using enzyme argininosuccinate synthetase (ASS). It has been observed that ASS is underexpressed in various types of cancers ASS, for which become auxotrophic. Arginine deiminase (ADI) a prokaryotic metabolizes to found inhibit melanoma hepatoma cancer deficient ASS. We tested hypothesis pancreatic have low expression therefore deprivation by ADI will cell growth. was examined 47 malignant 20 non‐neoplastic tissues as well panel human lines. achieved treatment with recombinant form formulated polyethylene glycol (PEG‐ADI). Effects on caspase activation, growth death were examined. Furthermore, effect PEG‐ADI vivo xenografts Eighty‐seven percent tumors lacked expression; 5 7 lines similarly expression. specifically inhibited those lacking induced activation induction apoptosis. tolerated mice despite complete elimination plasma arginine; tumor ∼50%. Reduced occurs predicts sensitivity treatment. Therefore, these findings suggest could provide beneficial strategy cancer, malignancy new therapy desperately needed. © 2008 Wiley‐Liss, Inc.