Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis
Abstract
:1. Introduction
2. Characteristics of the Cell Death-Switching Model System
3. Functional Analysis of Candidate Molecular Switches Regulating Necrosis and Apoptosis
4. Anticancer Strategy Targeting Cell Death Regulators of Necrotic to Apoptotic Cell Death
5. Conclusions and Future Directions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ATF3 | activating transcription factor 3 |
FUdR | floxuridine |
GA | geldanamycin |
HSP | heat shock protein |
miRNA | microRNA |
miR | miRNA |
siRNA | small interfering RNA |
TNF | tumor necrosis factor |
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Cell Line | F28-7 Cells | F28-7-A Cells |
---|---|---|
FUdR (EC50, nM) | 1 | 1 |
Cell death mode | Necrosis | Apoptosis |
Cell death morphological features | Swelling (Cell and organelles) | Membrane blebbing, shrinking (Cell and organelles) |
DNA fragmentation | Chromosome size (100–200 kbp) | Oligonucleosome size |
Mitochondrial events | ||
Membrane potential | Down | Down |
Cytochrome c release | - | + |
Cell death markers | ||
Caspase-3 | Cleaved | Cleaved |
PARP | Cleaved | Cleaved |
Extracellular HMGB1 | + | − |
Name | Expression | Cell Death | Experiments | Observation | Ref |
---|---|---|---|---|---|
HSP90 | NC | N > A | IH(GA) | MF, DL | [13] |
Lamin-B1 | High F28-7 | N > A | KD(siR) | MF | [15,16] |
Cytokeratin-19 | High F28-7 | N > A | KD(siR) | MF | [15] |
ATF3 | High F28-7 | N > A | KD(siR) | MF | [14] |
miR-351-5p | High F28-7-A | N > A/A > N | OE(miRm)/IH(miRi) | MF, HR | [49,51] |
miR-743a-3p | High F28-7-A | N > A | OE(miRm) | MF | [49] |
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Sato, A.; Hiramoto, A.; Kim, H.-S.; Wataya, Y. Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis. Int. J. Mol. Sci. 2020, 21, 5876. https://doi.org/10.3390/ijms21165876
Sato A, Hiramoto A, Kim H-S, Wataya Y. Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis. International Journal of Molecular Sciences. 2020; 21(16):5876. https://doi.org/10.3390/ijms21165876
Chicago/Turabian StyleSato, Akira, Akiko Hiramoto, Hye-Sook Kim, and Yusuke Wataya. 2020. "Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis" International Journal of Molecular Sciences 21, no. 16: 5876. https://doi.org/10.3390/ijms21165876