Human Recombinant Arginase I [HuArgI(Co)-PEG5000]–Induced Arginine Depletion Inhibits Pancreatic Cancer Cell Migration and Invasion Through Autophagy
| Autor: | Isabelle Fakhoury, Mirvat El-Sibai, Ralph J. Abi-Habib, Sarah Nohra, Nour El-Mais, Maria Al Haddad |
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| Rok vydání: | 2021 |
| Předmět: |
Programmed cell death
Arginase Hepatology Arginine Chemistry Endocrinology Diabetes and Metabolism Autophagy Cell migration Recombinant Proteins Polyethylene Glycols Pancreatic Neoplasms Focal adhesion Endocrinology Cell Movement Cell Line Tumor Invadopodia Cell Adhesion Internal Medicine Cancer research Humans Drug Screening Assays Antitumor Cell adhesion |
| Zdroj: | Pancreas. 50:1187-1194 |
| ISSN: | 1536-4828 0885-3177 |
| DOI: | 10.1097/mpa.0000000000001891 |
| Popis: | OBJECTIVES Pancreatic cancer is one of the most aggressive solid cancers and the fourth leading cause of cancer death in men and women. We previously showed that arginine depletion, using arginase I [HuArgI(Co)-PEG5000], selectively triggers cell death by autophagy in PANC-1 pancreatic cancer cells. The mechanism of action of [HuArgI(Co)-PEG5000], however, has remained poorly understood. In this study, we investigated the effects of arginine depletion on PANC-1 cell migration, adhesion, and invasion and determined the main molecular targets, which mediate PANC-1 cell response to treatment with HuArgI(Co)-PEG5000. METHODS This was done through examining 2-dimensional (2D) cell motility assays (wound healing and time lapse), cell adhesion, and cell invasion assays, as well as immunostaining for focal adhesions and invadopodia in cells without or with the treatment with arginase. RESULTS We demonstrate that arginine depletion decreases PANC-1 2D cell migration, adhesion, and 3D invasion. Moreover, our data suggest that these effects are mediated by autophagy and subsequent decrease in the activation of members of Ras homolog gene family (Rho) GTPase family. CONCLUSIONS Altogether, these findings uncover the mechanism of action of [HuArgI(Co)-PEG5000] and highlight the promising and selective anticancer potential for arginine depletion in the treatment of pancreatic cancer cells. |
| Databáze: | OpenAIRE |
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