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<p>In this study, we assess the activation of autophagy and its impact on cytotoxicity following [HuArgI (Co)-PEG5000]-induced arginine deprivation in AML cells. We have previously shown that arginine deprivation is selectively cytotoxic to AML cells and that cell death is caspase independent and non-apoptotic, hence the mechanism of cell death remained elusive. We tested a panel of 7 AML cell lines, and we first demonstrated that the cytotoxicity of [HuArgI (Co)-PEG5000] to AML cells is long-term and sustained despite re-expression of overexpression of ASS1 in all cell lines. We also demonstrated that arginine deprivation leads to a prolonged and extensive activation of autophagy starting at 24 and lasting up to 120&#xa0;h in all cells. Autophagy was shown to induce cell death since its inhibition using chloroquine (CQ) significantly decreased [HuArgI (Co)-PEG5000]-induced cytotoxicity, indicating autophagic cell death in AML cells following arginine deprivation. Moreover, we showed that arginine deprivation leads to ROS accumulation and that neutralizing ROS using N-acetylcysteine (NAC) does not affect the autophagic response but completely reverses the cytotoxicity of arginine deprivation, demonstrating that death by autophagy is dependent on ROS generation in AML cells.</p>

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Arginine deprivation induces ROS dependent autophagic cell death in human acute myeloid leukemia cells

  • 期刊论文

  • 发表日期：

    2026年3月30日

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  • Fatima Taki,
  • Mirna Farhat,
  • Oula El-Atat,
  • Sarah Al-Samman,
  • Nicole Assaf,
  • Ralph J. Abi-Habib

摘要

In this study, we assess the activation of autophagy and its impact on cytotoxicity following [HuArgI (Co)-PEG5000]-induced arginine deprivation in AML cells. We have previously shown that arginine deprivation is selectively cytotoxic to AML cells and that cell death is caspase independent and non-apoptotic, hence the mechanism of cell death remained elusive. We tested a panel of 7 AML cell lines, and we first demonstrated that the cytotoxicity of [HuArgI (Co)-PEG5000] to AML cells is long-term and sustained despite re-expression of overexpression of ASS1 in all cell lines. We also demonstrated that arginine deprivation leads to a prolonged and extensive activation of autophagy starting at 24 and lasting up to 120 h in all cells. Autophagy was shown to induce cell death since its inhibition using chloroquine (CQ) significantly decreased [HuArgI (Co)-PEG5000]-induced cytotoxicity, indicating autophagic cell death in AML cells following arginine deprivation. Moreover, we showed that arginine deprivation leads to ROS accumulation and that neutralizing ROS using N-acetylcysteine (NAC) does not affect the autophagic response but completely reverses the cytotoxicity of arginine deprivation, demonstrating that death by autophagy is dependent on ROS generation in AML cells.