tubacin and erastin

tubacin has been researched along with erastin* in 1 studies

Other Studies

1 other study(ies) available for tubacin and erastin

ArticleYear
HDAC6 inhibitors sensitize non-mesenchymal triple-negative breast cancer cells to cysteine deprivation.
    Scientific reports, 2021, 05-26, Volume: 11, Issue:1

    Triple-negative breast cancer (TNBC) is a highly malignant type of breast cancer and lacks effective therapy. Targeting cysteine-dependence is an emerging strategy to treat the mesenchymal TNBC. However, many TNBC cells are non-mesenchymal and unresponsive to cysteine deprivation. To overcome such resistance, three selective HDAC6 inhibitors (Tubacin, CAY10603, and Tubastatin A), identified by epigenetic compound library screening, can synergize with cysteine deprivation to induce cell death in the non-mesenchymal TNBC. Despite the efficacy of HDAC6 inhibitor, knockout of HDAC6 did not mimic the synthetic lethality induced by its inhibitors, indicating that HDAC6 is not the actual target of HDAC6 inhibitor in this context. Instead, transcriptomic profiling showed that tubacin triggers an extensive gene transcriptional program in combination with erastin, a cysteine transport blocker. Notably, the zinc-related gene response along with an increase of labile zinc was induced in cells by the combination treatment. The disturbance of zinc homeostasis was driven by PKCĪ³ activation, which revealed that the PKCĪ³ signaling pathway is required for HDAC6 inhibitor-mediated synthetic lethality. Overall, our study identifies a novel function of HDAC6 inhibitors that function as potent sensitizers of cysteine deprivation and are capable of abolishing cysteine-independence in non-mesenchymal TNBC.

    Topics: Anilides; Carbamates; Cell Death; Cell Line, Tumor; Cysteine; Enzyme Activation; Epithelial Cells; Female; Gene Knockout Techniques; HEK293 Cells; Histone Deacetylase 6; Histone Deacetylase Inhibitors; Homeostasis; Humans; Hydroxamic Acids; Indoles; Neoplasm Proteins; Oxazoles; Piperazines; Protein Kinase C; Small Molecule Libraries; Transcription, Genetic; Transcriptome; Triple Negative Breast Neoplasms; Zinc

2021