The combination of TRAIL and the Smac mimetic LCL-161 induces an irreversible phenotypic change of MCF-7 breast cancer cells

• DOI: 10.1016/j.yexmp.2021.104739
• Publication Date: 2022-01-07T15:48:16Z
• Authors: Victoria Granqvist; Christian Holmgren; Christer Larsson
• Keywords: MCF-7; Viability assay; XIAP

Breast cancer is the most common malignancy affecting women. Although prognosis generally good, a substantial number of patients still suffer from relapse, emphasizing need for novel treatments. Smac mimetics were developed to facilitate cell death by blocking inhibitor apoptosis proteins (IAPs). It has been suggested that TNF-related inducing ligand (TRAIL) can be used together with induce death. Cell viability was studied Trypan blue staining and Annexin V assay, siRNA downregulate specific proteins, protein levels estimated Western blot, mRNA analyzed qPCR, microarray RNA-seq. For global expression, groups compared principal component analysis limma package in R. Gene enrichment Fisher's test. other experiments, significance difference tested one-way ANOVA, followed Tukey's HSD The combination mimetic LCL-161 TRAIL induces an irreversible change phenotype, but not death, luminal MCF-7 breast cells. cells become small circular dissociate each effect could reversed returning regular growth medium. morphology prevented caspase inhibition using z-VAD-FMK downregulation caspase-8. Caspase-7 also indicated importance since this resulted fewer morphologically changed Enrichment analyses changes gene expression demonstrated genes associated estrogen receptor (ER) signaling are downregulated, whereas nuclear factor kappa B- (NF-κB) interferon- (IFN) driven upregulated altered However, these pathways did influence morphology. Induction IFN-induced potentiated NF-ĸB-driven slightly suppressed inhibition. results demonstrate irreversibly alter phenotype. mediated via separate pathways.