Abstract
In this study, we target arginine auxotrophy of AML cell lines using human arginase I cobalt-PEG5000. HuArgI(Co)-PEG5000 was cytotoxic to all AML cell lines tested. Mononuclear cells and CD34+ blasts were not sensitive demonstrating the selectivity of HuArgI(Co)-PEG5000-induced arginine deprivation. Addition of l-citrulline led to the rescue of five cell lines. The four cell lines that were not rescued by l-citrulline did not express argininosuccinate synthetase-1, indicating complete arginine auxotrophy. Inhibition of autophagy increased cell sensitivity to HuArgI(Co)-PEG5000 demonstrating the protective role of autophagy following arginine deprivation. We have shown that AML can be selectively targeted using HuArgI(Co)-PEG5000-induced arginine depletion.
Original language | English (US) |
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Pages (from-to) | 1565-1571 |
Number of pages | 7 |
Journal | Leukemia Research |
Volume | 37 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2013 |
Keywords
- AML
- Arginine
- Autophagy
- HuArgI(Co)-PEG5000
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research