Thymoquinone Is a Multitarget Single Epidrug That Inhibits the UHRF1 Protein Complex
Abstract
:1. Introduction
2. Role of the DNMT1/HDAC1/G9a Complex in Epigenetic Silencing of TSGs
3. A master Role for UHRF1 in the ECREM Complex Driving Epigenetic Inhibition of TSGs
4. UHRF1 Is a Main Target of Natural Compounds Exhibiting Anticancer Properties
5. The UHRF1 Protein Complex Is a Main Target of TQ
5.1. Inhibitory Effects of TQ on UHRF1
5.2. Inhibitory Effects of TQ on DNMT1 Expression and Activity
5.3. Inhibitory Effects of TQ on HDAC1
5.4. Inhibitory Effects of TQ on G9A
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Ethical Approval and Consent to Participate
Consent for publication
Abbreviations
DNMT1 | DNA methyltransferase 1 |
ECREM | Epigenetic Code Replication Machinery |
EGCG | Epigallocatechin-3-gallate |
HAUSP | Herpes virus-Associated Ubiquitin-Specific Protease |
HDAC1 | Histone deacetylase 1 |
PDE | Phosphodiesterase |
PHD | Plant Homeo Domain |
RING | Really Interesting New Gene domain |
SRA | Set and Ring Associated domain |
TSG | Tumor suppressor gene |
TQ | Thymoquinone |
TTD | Tandem Tudor Domain |
UBL | Ubiquitin-like domain |
UHRF1 | Ubiquitin-like with PHD and RING Finger domains 1 |
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Epi-Target | Role of Epi-Target | Experimental Model | Mechanisms of Action | References |
---|---|---|---|---|
UHRF1 | Reader | Human cervical carcinoma HeLa cells. T-ALL | TQ targeted the E3 ubiquitin ligase activity of UHRF1 resulting in an auto-ubiquitination of UHRF1 likely through the downregulation of HAUSP | [23] |
T-ALL | TQ upregulated p73 expression and cleaved caspase 3 leading to UHRF1 degradation | [63] | ||
T-ALL | TQ decreased the expression of PDE1A leading to the upregulation of p73 and downregulation of UHRF1 | [62] | ||
T-ALL Human breast cancer cells | TQ decreased the expression of mRNA UHRF1 in dose-dependent mechanism | [60] | ||
DNMT1 DNMT3A DNMT3B | Writer | Human acute myeloid leukemia cells Patient primary cells | TQ inhibited DNMT1 activity and decreased its expression through the disruption of Sp1/NFkB complex from DNMT1 promoter. TQ decreased the expression of DNMT3A through the upregulation of miR-29b, known to directly bind to the 3′-UTR of DNMT3A | [64] |
T-ALL | TQ decreased the expression of DNMT1 protein | [63] | ||
T-ALL | TQ decreased the expression of DNMT1, 3A,3B | [60] | ||
HDAC1 HDAC2 HDAC3 HDAC4 HDAC9 | Eraser | T-ALL | TQ decreased the expression of HDAC1 protein | [63] |
T-ALL | TQ decreased in the expression of HDAC1, 4 and 9 | [60] | ||
T-ALL Human breast cancer cells | TQ decreased the expression of mRNA HDAC1 in dose-dependent mechanism | [60] | ||
Human pancreatic ductal adenocarcinoma cells. Human pancreatic ductal adenocarcinoma xenografts. | TQ inhibited HDAC activity, decreased the expression of HDAC 1, 2, 3 at mRNA levels and increased the acetylation of histone 4 at lysine 12 (H4 Ac-K12) | [65] | ||
G9A | Writer | T-ALL Human breast cancer cells | TQ decreased the expression of mRNA G9A in dose-dependent mechanism | [60] |
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Abdullah, O.; Omran, Z.; Hosawi, S.; Hamiche, A.; Bronner, C.; Alhosin, M. Thymoquinone Is a Multitarget Single Epidrug That Inhibits the UHRF1 Protein Complex. Genes 2021, 12, 622. https://doi.org/10.3390/genes12050622
Abdullah O, Omran Z, Hosawi S, Hamiche A, Bronner C, Alhosin M. Thymoquinone Is a Multitarget Single Epidrug That Inhibits the UHRF1 Protein Complex. Genes. 2021; 12(5):622. https://doi.org/10.3390/genes12050622
Chicago/Turabian StyleAbdullah, Omeima, Ziad Omran, Salman Hosawi, Ali Hamiche, Christian Bronner, and Mahmoud Alhosin. 2021. "Thymoquinone Is a Multitarget Single Epidrug That Inhibits the UHRF1 Protein Complex" Genes 12, no. 5: 622. https://doi.org/10.3390/genes12050622
APA StyleAbdullah, O., Omran, Z., Hosawi, S., Hamiche, A., Bronner, C., & Alhosin, M. (2021). Thymoquinone Is a Multitarget Single Epidrug That Inhibits the UHRF1 Protein Complex. Genes, 12(5), 622. https://doi.org/10.3390/genes12050622