The SIRT2 Pathway Is Involved in the Antiproliferative Effect of Flavanones in Human Leukemia Monocytic THP-1 Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell-Free SIRT2 Histone Deacetylase Activity Assay
2.2. Drug Combination and Analysis of Synergistic Effect
2.3. Cell Culture
2.4. Cell Viability Assays
2.5. Cell Cycle Analysis
2.6. Quantification of Acetylated p53 in THP-1-Treated Cells
2.7. Real-Time PCR
2.8. Docking Studies
2.9. Statistical Analyses
3. Results
3.1. Flavanones Inhibited the Activity of the Isolated Recombinant SIRT2 Enzyme
3.2. NAR and HSP Acted Synergistically to Inhibit SIRT2 Enzymatic Activity
3.3. Flavanones Inhibited THP-1 Cell Proliferation
3.4. NAR and HSP Altered Cell Cycle Progression in THP-1 Cells
3.5. NAR and HSP Increased Levels of Acetylated p53 in THP-1 Cells
3.6. NAR and HSP Modulated SIRT2, p21, and Cyclin E1 but Not p53 mRNA Levels in THP-1 Cells
3.7. Flavanones Interacted with the Inhibitory Site of SIRT2 Enzyme
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | GenBank Accession Number | Primer Sequence |
SIRT2 | NM_012237.4 | Forward: 5′-TTCAAGCCAACCATCTGT-3′ Reverse: 5′-GTATCTATGTTCTGCGTGTAG-3′ |
TP53 | NM_000546.6 | Forward: 5′-GTGTGGAGTATTTGGATGAC-3′ Reverse: 5′-ATGTAGTTGTAGTGGATGGT-3′ |
CDKN1 | NM_000389.5 | Forward: 5′-TTCTCCACCTAGACTGTAA-3′ Reverse: 5′-GCACCTGCTGTATATTCA-3′ |
CCNE1 | NM_001238.4 | Forward: 5′-GGAAGAGGAAGGCAAACGTGA-3′ Reverse: 5′-TCGATTTTGGCCATTTCTTCAT-3′ |
ACTB | NM_001101.5 | Forward: 5′-TTGTTACAGGAAGTCCCTTGCC-3′ Reverse: 5′-ATGCTATCACCTCCCCTGTGTG-3′ |
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Russo, C.; Maugeri, A.; De Luca, L.; Gitto, R.; Lombardo, G.E.; Musumeci, L.; De Sarro, G.; Cirmi, S.; Navarra, M. The SIRT2 Pathway Is Involved in the Antiproliferative Effect of Flavanones in Human Leukemia Monocytic THP-1 Cells. Biomedicines 2022, 10, 2383. https://doi.org/10.3390/biomedicines10102383
Russo C, Maugeri A, De Luca L, Gitto R, Lombardo GE, Musumeci L, De Sarro G, Cirmi S, Navarra M. The SIRT2 Pathway Is Involved in the Antiproliferative Effect of Flavanones in Human Leukemia Monocytic THP-1 Cells. Biomedicines. 2022; 10(10):2383. https://doi.org/10.3390/biomedicines10102383
Chicago/Turabian StyleRusso, Caterina, Alessandro Maugeri, Laura De Luca, Rosaria Gitto, Giovanni Enrico Lombardo, Laura Musumeci, Giovambattista De Sarro, Santa Cirmi, and Michele Navarra. 2022. "The SIRT2 Pathway Is Involved in the Antiproliferative Effect of Flavanones in Human Leukemia Monocytic THP-1 Cells" Biomedicines 10, no. 10: 2383. https://doi.org/10.3390/biomedicines10102383