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.
Keywords: Endoplasmic Reticulum, histone deacetylase inhibitors, cell death, self-killing mechanisms, cancer therapy, canonical apoptotic, solid malignancies, cancer therapy
Current Pharmaceutical Biotechnology
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.
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Di Fazio Pietro, Ocker Matthias and Montalbano Roberta, New Drugs, Old Fashioned Ways: ER Stress Induced Cell Death, Current Pharmaceutical Biotechnology 2012; 13 (11) . https://dx.doi.org/10.2174/138920112802501962
DOI https://dx.doi.org/10.2174/138920112802501962 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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