Converting redox signaling to apoptotic activities by stress-responsive regulators HSF1 and NRF2 in fenretinide treated cancer cells.
<h4>Background</h4>Pharmacological intervention of redox balance in cancer cells often results in oxidative stress-mediated apoptosis, attracting much attention for the development of a new generation of targeted therapy in cancer. However, little is known about mechanisms underlying the...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | article |
| Language: | EN |
| Published: |
Public Library of Science (PLoS)
2009
|
| Subjects: | |
| Online Access: | https://doaj.org/article/8f9323f3746541df9de934bf541c36aa |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | <h4>Background</h4>Pharmacological intervention of redox balance in cancer cells often results in oxidative stress-mediated apoptosis, attracting much attention for the development of a new generation of targeted therapy in cancer. However, little is known about mechanisms underlying the conversion from oxidative signaling to downstream activities leading cells to death.<h4>Methodology/principal findings</h4>We here report a systematic detection of transcriptome changes in response to oxidative signals generated in leukemia cells upon fenretinide treatment, implicating the occurrence of numerous stress-responsive events during the fenretinide induced apoptosis, such as redox response, endoplasmic reticulum stress/unfolded protein response, translational repression and proteasome activation. Moreover, the configuration of these relevant events is primarily orchestrated by stress responsive transcription factors, as typically highlighted by NF-E2-related factor-2 (NRF2) and heat shock factor 1 (HSF1). Several lines of evidence suggest that the coordinated regulation of these transcription factors and thus their downstream genes are involved in converting oxidative signaling into downstream stress-responsive events regulating pro-apoptotic and apoptotic activities at the temporal and spatial levels, typifying oxidative stress-mediated programmed death rather than survival in cancer cells.<h4>Conclusions/significance</h4>This study provides a roadmap for understanding oxidative stress-mediated apoptosis in cancer cells, which may be further developed into more sophisticated therapeutic protocols, as implicated by synergistic induction of cell apoptosis using proteasome inhibitors with fenretinide. |
|---|