Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut 1102 2801, Lebanon.
Leuk Res. 2013 Nov;37(11):1565-71. doi: 10.1016/j.leukres.2013.08.007. Epub 2013 Aug 16.
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.
在这项研究中，我们使用人源精氨酸酶 I 钴-PEG5000 靶向 AML 细胞系的精氨酸营养缺陷型。HuArgI(Co)-PEG5000 对所有测试的 AML 细胞系均具有细胞毒性。单核细胞和 CD34(+) blasts 不敏感，表明 HuArgI(Co)-PEG5000 诱导的精氨酸剥夺具有选择性。添加 L-瓜氨酸可导致 5 种细胞系的恢复。不能被 L-瓜氨酸挽救的 4 种细胞系不表达精氨琥珀酸合成酶-1，表明完全的精氨酸营养缺陷型。自噬的抑制增加了细胞对 HuArgI(Co)-PEG5000 的敏感性，表明自噬在精氨酸剥夺后具有保护作用。我们已经表明，AML 可以使用 HuArgI(Co)-PEG5000 诱导的精氨酸耗竭来选择性靶向。
