PEG-BCT-100 and Canavanine Synergistically Induce Apoptosis in Arginine Biosynthetic Enzyme-Deficient Pancreatic Cancer.

ABSTRACT:

Abstract

Arginine deprivation using arginase emerges as a potential cancer treatment approach, as some cancers have been found to be arginine-auxotrophic, relying on exogenous arginine for their growth. In this study, we evaluated the combination of a PEGylated recombinant human arginase (PEG-BCT-100), which is currently undergoing clinical trials, with a toxic arginine analog, canavanine, in pancreatic cancer. Remarkable synergistic antitumor effect was observed both in vitro and in vivo. Specifically, the combination treatment induced apoptotic cell death in pancreatic cancer cells, whereas normal fibroblast cells remained viable. Our findings also suggested that pancreatic tumors lacking the key enzymes in arginine biosynthesis, argininosuccinate synthetase 1 (ASS1) and ornithin

SUBMITTER: Kwong TT 

PROVIDER: S-EPMC11695075 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature