Antagonizing RARγ Drives Necroptosis of Cancer Stem Cells
Abstract
:1. Introduction
2. Why Target RARγ to Eliminate CSCs?
2.1. The Role of RARγ within Stem Cells
2.2. RARγ Is an Oncogene for a Number of Cancers
2.3. PCa Cells Are Dependent on Active RARγ for Their Survival
3. Agonists and Antagonists of RARs
4. Antagonizing RARγ Kills CSCs
5. Antagonizing All RARs Is Effective against Pediatric Brain Tumors
6. The Effect of Antagonizing RARs on Normal Cells
7. Concluding Remarks
8. Perspectives
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Retinoids | RARα | RARβ | RARγ | Classification |
---|---|---|---|---|
RAR Agonists—Equilibrium Binding Affinities in nM | ||||
ATRA | ND | ND | ND | RARαβγ |
AGN195183 | 20.1 | >5000 | >5000 | RARα |
AGN190168 | >1000 | 14.2 | 135 | RARβγ |
AGN205327 | 3700 | 734 | 32 | RARγ |
RAR Antagonists—Equilibrium Binding Affinities in nM | ||||
AGN194310 | 4.3 | 5 | 2 | RARαβγ |
AGN196996 | 3.9 | 4036 | >10,000 | RARα |
AGN194431 | 300 | 6 | 20 | RARβγ |
AGN205728 | 2400 | 4248 | 3 | RARγ |
Cells | AGN194310 pan-RAR Antagonist IC50 Values | AGN193109 pan-RAR Antagonist IC50 Values | AGN193776 pan-RAR Antagonist IC50 Values | LG100815 pan-RAR Antagonist IC50 Values | AGN205728 RARγ Antagonist IC50 Values |
---|---|---|---|---|---|
PCa cells | |||||
DU-145 | 5. 0 × 10−7 M | 1.8 × 10−6 M | 6.0 × 10−7 M | ||
LNCaP | 4.0 × 10−7 M | 4.2 × 10−7 M | 3.9 × 10−7 M | 5.2 × 10−7 M | 4.5 × 10−7 M |
PC-3 | 3.5 × 10−7 M | 6.8 × 10−7 M | 5.7 × 10−7 M | 1.0 × 10−6 M | 4.7 × 10−7 M |
Patients’ cells | 4.7 ± 2.1 × 10−7 M * | 3.0 × 10−7 M | |||
Non-malignant prostate cells | |||||
Prostate epithelial | 1.0 × 10−6 M | 1.4 × 10−6 M | 1.1 × 10−6 M | >1 × 10−5 M | 7.2 × 10−7 M |
RWPE-1 | 2.3 × 10−6 M |
PCa Lines | AGN194310 pan-RAR Antagonist IC50 Values | AGN205728 RARγ Antagonist IC50 Values | AGN196996 RARα Antagonist IC50 Values | ATRA pan-RAR Agonist IC50 Values |
---|---|---|---|---|
DU-145 | 34 × 10−9 M | 60 × 10−9 M | >1 × 10−5 M | 4.0 × 10−7 M |
LNCaP | 16 × 10−9 M | 55 × 10−9 M | >1 × 10−5 M | 3.2 × 10−7 M |
PC-3 | 18 × 10−9 M | 50 × 10−9 M | >1 × 10−5 M | 4.2 × 10−7 M |
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Brown, G. Antagonizing RARγ Drives Necroptosis of Cancer Stem Cells. Int. J. Mol. Sci. 2022, 23, 4814. https://doi.org/10.3390/ijms23094814
Brown G. Antagonizing RARγ Drives Necroptosis of Cancer Stem Cells. International Journal of Molecular Sciences. 2022; 23(9):4814. https://doi.org/10.3390/ijms23094814
Chicago/Turabian StyleBrown, Geoffrey. 2022. "Antagonizing RARγ Drives Necroptosis of Cancer Stem Cells" International Journal of Molecular Sciences 23, no. 9: 4814. https://doi.org/10.3390/ijms23094814