Overexpression of Human ABCB1 and ABCG2 Reduces the Susceptibility of Cancer Cells to the Histone Deacetylase 6-Specific Inhibitor Citarinostat
Abstract
:1. Introduction
2. Results
2.1. Citarinostat Is Less Cytotoxic in Cells Overexpressing ABCB1 or ABCG2
2.2. The Effect of Citarinostat on the Activity of HDAC6 Is Reduced by ABCB1 and ABCG2 in Human Cancer Cell Lines
2.3. The Intracellular Accumulation of Citarinostat Is Reduced by ABCB1 and ABCG2 in Human Cancer Cell Lines
2.4. Docking of Citarinostat in the Drug-Binding Pocket of ABCB1 and ABCG2
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. Cell Lines and Culture Conditions
4.3. Cytotoxicity Assays
4.4. Immunoblot
4.5. Apoptosis Assays
4.6. Citarinostat Accumulation Assay and HPLC-MS/MS Analysis
4.7. Docking of Citarinostat in the Substrate-Binding Pocket of Human ABCB1 and ABCG2
4.8. Quantification and Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Cell Line | Mean IC50 ± SD [μM] 1 (R.F 2) | ||
---|---|---|---|
Citarinostat | Citarinostat + Tariquidar | Citarinostat + Ko143 | |
KB-3-1 | 3.98 ± 0.73 (1) | 4.59 ± 0.67 (1) | N.D |
KB-V-1 | 57.96 ± 5.56 (15) | 3.01 ± 0.57 *** (1) | N.D |
OVCAR-8 | 7.52 ± 1.10 (1) | 7.46 ± 1.55 (1) | N.D |
NCI-ADR-RES | 84.15 ± 9.91 (11) | 5.56 ± 1.10 *** (1) | N.D |
S1 | 2.82 ± 0.40 (1) | N.D | 2.75 ± 0.45 (1) |
S1-M1-80 | 59.66 ± 10.32 (21) | N.D | 2.94 ± 0.50 *** (1) |
H460 | 7.46 ± 0.36 (1) | N.D | 6.17 ± 0.53 * (1) |
H460-MX20 | 23.70 ± 1.58 (3) | N.D | 6.08 ± 0.36 *** (1) |
pcDNA-HEK293 | 3.01 ± 0.44 (1) | 2.18 ± 0.21 (1) | 1.57 ± 0.20 ** (1) |
MDR19-HEK293 | 33.83 ± 3.21 (11) | 3.19 ± 0.21 *** (1) | N.D |
R482-HEK293 | 20.11 ± 2.48 *** (7) | N.D | 4.78 ± 0.37 *** (3) |
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Wu, C.-P.; Hung, C.-Y.; Lusvarghi, S.; Chang, Y.-F.; Hsiao, S.-H.; Huang, Y.-H.; Hung, T.-H.; Yu, J.-S.; Ambudkar, S.V. Overexpression of Human ABCB1 and ABCG2 Reduces the Susceptibility of Cancer Cells to the Histone Deacetylase 6-Specific Inhibitor Citarinostat. Int. J. Mol. Sci. 2021, 22, 2592. https://doi.org/10.3390/ijms22052592
Wu C-P, Hung C-Y, Lusvarghi S, Chang Y-F, Hsiao S-H, Huang Y-H, Hung T-H, Yu J-S, Ambudkar SV. Overexpression of Human ABCB1 and ABCG2 Reduces the Susceptibility of Cancer Cells to the Histone Deacetylase 6-Specific Inhibitor Citarinostat. International Journal of Molecular Sciences. 2021; 22(5):2592. https://doi.org/10.3390/ijms22052592
Chicago/Turabian StyleWu, Chung-Pu, Cheng-Yu Hung, Sabrina Lusvarghi, Yen-Fu Chang, Sung-Han Hsiao, Yang-Hui Huang, Tai-Ho Hung, Jau-Song Yu, and Suresh. V. Ambudkar. 2021. "Overexpression of Human ABCB1 and ABCG2 Reduces the Susceptibility of Cancer Cells to the Histone Deacetylase 6-Specific Inhibitor Citarinostat" International Journal of Molecular Sciences 22, no. 5: 2592. https://doi.org/10.3390/ijms22052592