Title:New Drugs, Old Fashioned Ways: ER Stress Induced Cell Death
Volume: 13
Issue: 11
Author(s): Pietro Di Fazio, Matthias Ocker and Roberta Montalbano
Affiliation:
Keywords:
Endoplasmic Reticulum, histone deacetylase inhibitors, cell death, self-killing mechanisms, cancer therapy, canonical apoptotic, solid malignancies, cancer therapy
Abstract: Discovery of small molecules able to induce several cellular self-killing mechanisms improved cancer therapy
in the last years. Research focused on canonical apoptotic (mitochondria or death receptor related) pathways to induce cell
death in several hematologic and solid malignancies, showing that treatment with different synthetic and natural compounds
reactivates the cell death machinery previously silenced in resistant cancer cells. Besides the canonical apoptotic
pathways, alternative pathways of cell death induction have recently been rediscovered as potential new targets for cancer
therapy. Under certain conditions, protein folding can be disturbed causing an accumulation of unfolded proteins inside
the endoplasmic reticulum (ER). This situation leads to stress ER, involving the transcriptional and translational machinery
to induce the expression and post-transcriptional modifications of many factors involved in ER stress response mediated
cell death. In this scenario, some apoptotic players like caspase 4 or caspase 12 start to control cell fate by inducing
downstream cell death proteins. Recently, inhibitors of protein deacetylases have been demonstrated to potently induce
this alternative cell death pathway and will be reviewed here.
