Human recombinant arginase I (Co)-PRG5000 [HuArgl (Co)-PRG5000]- induced arginine depletion selectively inhibits colon cancer cell migration and invasion. (c2018)

Abstract

Many arginine deprivation studies have been done on different cancer cell lines to understand the complete mechanisms of HuArgI(Co)-PEG5000. Colorectal cancer is the third most common type of cancer worldwide, and it represents over half of all gastrointestinal cancer death. Therefore, the first purpose of this study is to examine the cytotoxic effect of HuArgI(Co)-PEG5000 on colorectal cancer cell lines (HT-29, Caco-2, Sw837, Sw1116, SKco-1). The second aim is to investigate the effect of arginase depletion on colorectal cancer cell line Caco-2 metastatic and invasive abilities. This is achieved by performing cytotoxicity, 2D and 3D migration assays, western immunoblotting, immunostaining, and Förster Resonance energy transfer. Analysis of the results show that HuArgI(Co)-PEG5000 downregulates ASS1 and RhoA expression levels while it also downregulates cell migration, adhesion, and invasion in Caco-2 cell lines. However, L-citrulline can significantly restore arginine levels and hence counter the effect of HuArgI(Co)-PEG5000. Therefore, we can conclude that colorectal cancer is partial auxotrophic to arginine depletion and that arginine depletion plays an important role in regulating cancer cells motility and invasion.