The Antianginal Drug Perhexiline Displays Cytotoxicity against Colorectal Cancer Cells In Vitro: A Potential for Drug Repurposing
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Reagents
2.2. Cell Lines and Culture
2.3. Patient-Derived Organoids
2.4. Crystal Violet Viability Assay
2.5. Apoptosis Assay by Annexin V/Propidium Iodide Staining
2.6. Caspase 3/7 Activation Assay
2.7. AlamarBlue Viability Assay for Patient-Derived Organoids
2.8. Statistical Analysis
3. Results
3.1. Effect of Perhexiline and Its Enatiomers on CRC Monolayer Growth
3.2. Effect of Perhexiline and Its Enantiomers on Annexin V Induction
3.3. Kinetics of Apoptosis Induction by Perhexiline and Its Enantiomers
3.4. Effect of Perhexiline and Its Enantiomers on CRC Spheroids
3.5. Effect of Perhexiline and Its Enantiomers on Patient-Derived CRC Organoids
4. Discussion
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 | Cell Type | (−)-P | (+)-P | (R)-P |
---|---|---|---|---|
COLO205 | CRC | 4.27 ± 0.51 | 4.39 ± 0.47 | 3.29 ± 0.90 |
HCT116 | CRC | 3.37 ± 0.82 | 5.01 ± 1.91 | 3.45 ± 0.74 |
HT29 | CRC | 3.81 ± 1.00 | 4.25 ± 0.32 | 3.08 ± 0.41 |
SW480 | CRC | 3.70 ± 1.30 | 3.92 ± 0.74 | 3.92 ± 0.99 |
SW620 | CRC | 3.88 ± 0.48 | 4.30 ± 0.70 | 3.62 ± 0.91 |
HFF | Fibroblast | 11.06 ± 1.04 | 12.04 ± 0.53 | 11.34 ± 0.85 |
Cell Line | (−)-P | (+)-P | (R)-P |
---|---|---|---|
COLO205 | 2.59 | 2.74 | 3.45 |
HCT116 | 3.28 | 2.40 | 3.29 |
HT29 | 2.90 | 2.83 | 3.68 |
SW480 | 2.99 | 3.07 | 2.89 |
SW620 | 2.85 | 2.80 | 3.13 |
Sample | Sex | Age | Location | Stage | Primary/Metastasis | MMR * | IC50 (µM) | ||
---|---|---|---|---|---|---|---|---|---|
(−)-P | (+)-P | (R)-P | |||||||
TQEH 196 | M | 59 | Liver | T4 | Metastasis | MSS | 3.23 | 3.82 | 4.76 |
TQEH 198 | M | 68 | Liver | T4 | Metastasis | MSS | 1.36 | 2.87 | 3.78 |
SAH01 | F | 50 | Lung | T4 | Metastasis | MSS | 1.23 | 1.36 | 1.95 |
RAH038 | F | 87 | Colon (Ascending) | T3 | Primary | MSI (Absent MLH1 and PMS2) | 4.38 | 4.48 | 3.93 |
RAH057 | F | 65 | Colon (Sigmoid) | T3 | Primary | MSS | 2.62 | 2.81 | 3.28 |
RAP05 | M | 71 | Colon (Caecum) | T3 | Primary | MSS | 3.36 | 3.25 | 4.93 |
RAH51 | F | 82 | Colon (Hepatic Flexure) | T4 | Primary | MSI (Absent MLH1 and PMS2) | 1.91 | 2.07 | 2.80 |
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Dhakal, B.; Li, C.M.Y.; Li, R.; Yeo, K.; Wright, J.A.; Gieniec, K.A.; Vrbanac, L.; Sammour, T.; Lawrence, M.; Thomas, M.; et al. The Antianginal Drug Perhexiline Displays Cytotoxicity against Colorectal Cancer Cells In Vitro: A Potential for Drug Repurposing. Cancers 2022, 14, 1043. https://doi.org/10.3390/cancers14041043
Dhakal B, Li CMY, Li R, Yeo K, Wright JA, Gieniec KA, Vrbanac L, Sammour T, Lawrence M, Thomas M, et al. The Antianginal Drug Perhexiline Displays Cytotoxicity against Colorectal Cancer Cells In Vitro: A Potential for Drug Repurposing. Cancers. 2022; 14(4):1043. https://doi.org/10.3390/cancers14041043
Chicago/Turabian StyleDhakal, Bimala, Celine Man Ying Li, Runhao Li, Kenny Yeo, Josephine A. Wright, Krystyna A. Gieniec, Laura Vrbanac, Tarik Sammour, Matthew Lawrence, Michelle Thomas, and et al. 2022. "The Antianginal Drug Perhexiline Displays Cytotoxicity against Colorectal Cancer Cells In Vitro: A Potential for Drug Repurposing" Cancers 14, no. 4: 1043. https://doi.org/10.3390/cancers14041043
APA StyleDhakal, B., Li, C. M. Y., Li, R., Yeo, K., Wright, J. A., Gieniec, K. A., Vrbanac, L., Sammour, T., Lawrence, M., Thomas, M., Lewis, M., Perry, J., Worthley, D. L., Woods, S. L., Drew, P., Sallustio, B. C., Smith, E., Horowitz, J. D., Maddern, G. J., ... Fenix, K. (2022). The Antianginal Drug Perhexiline Displays Cytotoxicity against Colorectal Cancer Cells In Vitro: A Potential for Drug Repurposing. Cancers, 14(4), 1043. https://doi.org/10.3390/cancers14041043