Oxidative stress induced by the tetrahydrobenzimidazole TMQ0153 modulates crosstalk between apoptosis, autophagy and necroptosis in chronic myeloid leukemia - Part 2 (Figure2, 3, 4a)

Published: 4 Oct 2019 | Version 3 | DOI: 10.17632/htg4vdkmvv.3
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Description of this data

Aims: We demonstrate the capacity of the cytotoxic synthetic tetrahydrobenzimidazole (TMQ) hydroquinone (HQ) derivative TMQ0153 to induce reactive oxygen species (ROS) and mediate differential cell death modalities in chronic myeloid leukemia (CML).
Results: Results showed that concentrations of TMQ0153 < 20 µM trigger apoptosis, whereas concentrations > 30 µM lead to ROS-mediated necrostatin-sensitive necroptosis. Moreover, TMQ0153 allowed us to elucidate the interplay of ROS-mediated cell death and cell stress/survival mechanisms as this compound triggers protective autophagy in response to metabolic stress in CML cells. Importantly, the modulation of cell stress prior to TMQ0153-induced cell death enhances the exposure of “find-me”/“eat-me” signals considered as hallmarks of immunogenic cell death (ICD), altogether providing a pro-oxidant therapeutic strategy against CML.
Innovation: We suggest here a pro-oxidant anti-CML therapy leading to differential cell death modalities in both imatinib-sensitive and -resistant CML cell types. Moreover, we elucidated the interplay between apoptosis, autophagy and controlled necrosis induced by TMQ0153 leading to disruption of mitochondrial homeostasis.
Conclusion: Our findings indicate that TMQ0153-induced ROS act as a rheostat determining the onset of apoptotic- or autophagy-related controlled necrotic cell death in CML.

Experiment data files

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Latest version

  • Version 3

    2019-10-04

    Published: 2019-10-04

    DOI: 10.17632/htg4vdkmvv.3

    Cite this dataset

    Song, Sungmi (2019), “Oxidative stress induced by the tetrahydrobenzimidazole TMQ0153 modulates crosstalk between apoptosis, autophagy and necroptosis in chronic myeloid leukemia - Part 2 (Figure2, 3, 4a)”, Mendeley Data, v3 http://dx.doi.org/10.17632/htg4vdkmvv.3

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