Human recombinant arginase I(Co)-PEG5000 [HuArgI(Co)-PEG5000]-induced arginine depletion is selectively cytotoxic to human acute myeloid leukemia cells

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• 作者：Rita Tanios ; Amira Bekdash ; Elias Kassab ; Everett Stone ; Georges Georgiou ; Arthur E. Frankel ; Ralph J. Abi-Habib
• 关键词：HuArgI(Co)-PEG5000 ; AML ; Arginine ; Autophagy
• 刊名：Leukemia Research
• 出版年：November, 2013
• 年：2013
• 卷：37
• 期：11
• 页码：1565-1571
• 全文大小：1619 K

文摘

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.