00085472can093537-sup-sfi_g2.pdf (124.57 kB)
Supplementary Figure 2 from Resveratrol Promotes Autophagic Cell Death in Chronic Myelogenous Leukemia Cells via JNK-Mediated p62/SQSTM1 Expression and AMPK Activation
journal contribution
posted on 2023-03-30, 20:12 authored by Alexandre Puissant, Guillaume Robert, Nina Fenouille, Frederic Luciano, Jill-Patrice Cassuto, Sophie Raynaud, Patrick AubergerSupplementary Figure 2 from Resveratrol Promotes Autophagic Cell Death in Chronic Myelogenous Leukemia Cells via JNK-Mediated p62/SQSTM1 Expression and AMPK Activation
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ARTICLE ABSTRACT
Autophagy that is induced by starvation or cellular stress can enable cancer cell survival by sustaining energy homeostasis and eliminating damaged organelles and proteins. In response to stress, cancer cells have been reported to accumulate the protein p62/SQSTM1 (p62), but its role in the regulation of autophagy is controversial. Here, we report that the plant phytoalexin resveratrol (RSV) triggers autophagy in imatinib-sensitive and imatinib-resistant chronic myelogenous leukemia (CML) cells via JNK-dependent accumulation of p62. JNK inhibition or p62 knockdown prevented RSV-mediated autophagy and antileukemic effects. RSV also stimulated AMPK, thereby inhibiting the mTOR pathway. AMPK knockdown or mTOR overexpression impaired RSV-induced autophagy but not JNK activation. Lastly, p62 expression and autophagy in CD34+ progenitors from patients with CML was induced by RSV, and disrupting autophagy protected CD34+ CML cells from RSV-mediated cell death. We concluded that RSV triggered autophagic cell death in CML cells via both JNK-mediated p62 overexpression and AMPK activation. Our findings show that the JNK and AMPK pathways can cooperate to eliminate CML cells via autophagy. Cancer Res; 70(3); 1042–52Usage metrics
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Keywords
CarcinogenesisSignal transductionCell SignalingDrug Discovery TechnologiesNatural productsDrug MechanismsDrug-mediated stimulation of cell death pathwaysDrug ResistanceClinical drug resistanceDrug TargetsGene RegulationPhosphorylation and gene expressionHematological CancersLeukemiasSmall Molecule Agents