Bioengineered arginase I increases caspase-3 expression of hepatocellular and pancreatic carcinoma cells despite induction of argininosuccinate synthe tase-1

Background. Hepatocellular and pancreatic carcinomas are often auxotrophic for L-arginine, a semi-essential amino acid The purpose of this study was to investigate cancer cell death using a significantly more active, cobalt-substituted bioengineered arginase. Methods. Panc-1, a human pancreatic carcinoma cell line, and Hep 3B, a human hepatocellular carcinoma cell line, were exposed to L-arginase Row cytometry was used to measure expression of Ki-67, caspase-3, and argininosuccinate synthetase-1 (ASS-1) 4 days after treatment An MTT assay measured proliferation. The Student I test determined statistical significance Results. Viability decreased by 31% +/- 2% for Panc-1 cells (P < .0001) and 34% +/- 1% (P < 0001) for Hep 311 cells after treatment Both cell lines demonstrated a 4-fold increase activated caspase-3 expression. after high dose treatment (P < 01), and 5-fold increase in ASS-1 expression (P < .002) Ki-67 expression did not vary in Hep 313 cells but decreased for Panc-1 cells (P < 015) The 50% inhibitory concentration was 8-fold higher for Pane-1 cells than for Hep 313 cells (P < .03) Conclusion. Increased ASS-1 expression by these cells, in order to increase L-arginine concentration., is inadequate, suggesting a mechanism by which arginine depletion. can be used in multimodality therapy for arginine-dependent cancers (Surgery 2010,148 310-8.)