PMID- 16356828 OWN - NLM STAT- MEDLINE DCOM- 20060224 LR - 20131121 IS - 0304-3835 (Print) IS - 0304-3835 (Linking) VI - 231 IP - 1 DP - 2006 Jan 8 TI - Modulation of arginine metabolic pathways as the potential anti-tumor mechanism of recombinant arginine deiminase. PG - 30-5 AB - Arginine deiminase (ADI), currently in clinical trials, has various biological activities including anti-proliferation, anti-angiogenesis and inhibition of inducible nitric oxide synthase (iNOS). To recognize limitations and therapeutic applications, the mechanism of ADI modulation of arginine metabolic pathways was investigated. MCF-7 and A549 cells have notable different sensitivity to recombinant ADI (rADI) and express diverse argininosuccinate synthase (AS) activity, which regenerates arginine. Due to compartmentalization of arginine, utilization of arginine for protein synthesis occurs from either the intracellular arginine pool or the citrulline-arginine-regeneration pathway, whereas for polyamine synthesis, utilization is only from the intracellular arginine pool. Modulating AS activity or introducing rADI intracellularly to reduce intracellular arginine regeneration may expand therapeutic applications of rADI. FAU - Shen, Li-Jiuan AU - Shen LJ AD - Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, 404B, Los Angeles, CA 90089-9121, USA. FAU - Beloussow, Karin AU - Beloussow K FAU - Shen, Wei-Chiang AU - Shen WC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Cancer Lett JT - Cancer letters JID - 7600053 RN - 0 (Polyamines) RN - 31C4KY9ESH (Nitric Oxide) RN - 94ZLA3W45F (Arginine) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 3.- (Hydrolases) RN - EC 3.5.3.6 (arginine deiminase) SB - IM MH - Adenocarcinoma/pathology MH - Arginine/*metabolism MH - Breast Neoplasms/pathology MH - Humans MH - Hydrolases/*pharmacology MH - Lung Neoplasms/pathology MH - Neoplasms/drug therapy MH - Nitric Oxide MH - Nitric Oxide Synthase/metabolism MH - Polyamines MH - Protein Biosynthesis/*drug effects MH - Tumor Cells, Cultured EDAT- 2005/12/17 09:00 MHDA- 2006/02/25 09:00 CRDT- 2005/12/17 09:00 PHST- 2004/08/13 00:00 [received] PHST- 2004/12/02 00:00 [revised] PHST- 2005/01/07 00:00 [accepted] PHST- 2005/12/17 09:00 [pubmed] PHST- 2006/02/25 09:00 [medline] PHST- 2005/12/17 09:00 [entrez] AID - S0304-3835(05)00040-6 [pii] AID - 10.1016/j.canlet.2005.01.007 [doi] PST - ppublish SO - Cancer Lett. 2006 Jan 8;231(1):30-5. doi: 10.1016/j.canlet.2005.01.007.