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Human Recombinant Arginase I HuArgI (Co)-PEG5000-Induced Arginine Depletion Inhibits Colorectal Cancer Cell Migration and Invasion
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Human Recombinant Arginase I HuArgI (Co)-PEG5000-Induced Arginine Depletion Inhibits Colorectal Cancer Cell Migration and Invasion
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Human Recombinant Arginase I HuArgI (Co)-PEG5000-Induced Arginine Depletion Inhibits Colorectal Cancer Cell Migration and Invasion
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Journal Article
Human Recombinant Arginase I HuArgI (Co)-PEG5000-Induced Arginine Depletion Inhibits Colorectal Cancer Cell Migration and Invasion
2019
Overview
Purpose: Colorectal cancer (CRC) is the third most common type of cancer worldwide, and it represents over half of all gastrointestinal cancer deaths. Knowing that cancer cells have a high proliferation rate, they require high amounts of amino acids, including arginine. In addition, several tumor types have been shown to downregulate ASS-1 expression, becoming auxotrophic for arginine. Therefore, Arginine deprivation is one of the promising therapeutic approaches to target cancer cells. This can be achieved through the use of a recombinant human arginase, HuArgI(Co)-PEG5000, an arginine degrading enzyme. Methods: In this present study, the cytotoxic effect of HuArgI(Co)-PEG5000 on CRC cell lines (HT-29, Caco-2, Sw837) is examined though cytotoxicity assays. Wound healing assays, invasion assays, and adhesion assays were also performed to detect the effect on metastasis. Results: Wound healing and invasion assays revealed a decrease in cell migration and invasion after treatment with arginase. Cells that were treated with arginase also showed a decrease in adhesion, which coincided with a decrease in RhoA activation, demonstrated though the use of a FRET biosensor to detect RhoA activation in a single cell assay, and a decrease in MMP-9 expression. Treating cells with both arginase and L-citrulline, which significantly restores intracellular arginine levels, reversed the effect of HuArgI(Co)-PEG5000 on cell viability, migration, and invasion. Conclusion: We can, therefore, conclude that colorectal cancer is partially auxotrophic to arginine and that arginine depletion is a potential selective inhibitory approach for motility and invasion in colon cancer cells.
Publisher
MDPI AG,MDPI
Subject
Antineoplastic Agents - pharmacology
/ Cell Movement - drug effects
/ Cell Survival - drug effects
/ Colorectal Neoplasms - drug therapy
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - pathology
/ Enzymes
/ Humans
/ Leukemia
/ Motility
/ Neoplasm Invasiveness - pathology
/ Neoplasm Invasiveness - prevention & control
