Arginine Is a Novel Drug Target for Arginine Decarboxylase in Human Colorectal Cancer Cells

Abstract

Colorectal cancer (CRC) has been proven to be highly reliant on arginine availability. Limiting arginine-rich foods or treating patients with arginine-depleting enzymes arginine deiminase (ADI) or arginase can suppress colon cancer. However, arginase and ADI are not the best drug candidates for CRC. Ornithine, the product of arginase, can enhance the supply of polyamine, which favors CRC cell growth, while citrulline, the product of ADI, faces the problem of arginine recycling due to the overexpression of argininosuccinate synthetase (ASS). Biosynthetic arginine decarboxylase (ADC), an enzyme that catalyzes the conversion of arginine to agmatine and carbon dioxide, may be a better choice as it combines both arginine depletion and suppression of intracellular polyamine synthesis via its product agmatine. ADC has anti-tumor potential yet has received much less attention than the other two arginine-depleting enzymes. In order to gain a better understanding of ADC, the preparation and the anti-cancer properties of this enzyme were explored in this study. When tested in vitro, ADC inhibited the proliferation of three colorectal cancer cell lines regardless of their ASS cellular expression. In contrast, ADC had a lesser cytotoxic effect on the human foreskin fibroblasts and rat primary hepatocytes. Further in vitro studies revealed that ADC induced S and G2/M phase cell-cycle arrest and apoptosis in HCT116 and LoVo cells. ADC-induced apoptosis in HCT116 cells followed the mitochondrial apoptotic pathway and was caspase-3-dependent. With all results obtained, we suggest that arginine is a potential target for treating colorectal cancer with ADC, and the anti-cancer properties of ADC should be more deeply investigated in the future.

Isolation and identification of bacterial isolates producing Arginine deiminase from assorted soil environments in Egypt using16S rRNA sequencing technique

“…Based on the L-citrulline standard curve, which was determined using the same technique, the amount of Citrulline was computed and associated with the activity of the ADI enzyme, which converted L-arginine to L-citrulline. 22 Identi cation of the major bacterial isolate producing ADI: This was performed using Gram staining technique and different biochemical reactions; as well as the determination of morphological characters and molecular detection using 16S rRNA sequencing technique were employed. The genomic DNA was extracted using PureLink™ genomic DNA Puri cation kit( purchased from ThermoFisher scienti c, USA) on Silica Columns.…”