Oleocanthal Attenuates Metastatic Castration-Resistant Prostate Cancer Progression and Recurrence by Targeting SMYD2
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Cell Lines and Culture Conditions
2.3. Experimental Treatments
2.4. Cell Viability Assay
2.5. CRISPR-Cas9 SMYD2 Knockout (KO)
2.6. Wound-Healing Assay
2.7. Colony Formation Assay
2.8. Transwell Migration Assay
2.9. Invasion Assay
2.10. Western Blot Analysis
2.11. Lentivirus Transduction-Aided Luciferase Labeling of CWR-R1ca Cells
2.12. Animal Models and Treatment
2.12.1. OC Suppressed mCRPC CWR-R1ca-Luc Cell Progression In Vivo in Nude Mouse Model
2.12.2. Oral Treatments with OC-PF Effectively Suppressed mCRPC CWR-R1ca-Luc Cells’ Recurrence in Nude Mouse Model after Primary Tumor Surgical Excision
2.13. Quantification of PSA Serum Levels Using ELISA Kit
2.14. Immunohistochemistry (IHC) Study
2.15. Hematoxylin and Eosin Y (H&E) Staining
2.16. Analysis of Clinical SMYD2 Gene Expression Data
2.17. Statistics
3. Results
3.1. Prognosis Analysis of SMYD Family mRNA Expression in Prostate Cancer Patients
3.2. Prognostic Analysis of SMYD2 mRNA Expression in PC Patients
3.3. Exploration of SMYD2 Expression Pattern in PC and Non-Tumorigenic RWPE-1 Prostatic Epithelial Cells
3.4. SMYD2 Is Essential for mCRPC Cell Survival and Motility
3.5. OC Inhibited SMYD2 Monomethylation in Biochemical Assays
3.6. OC Treatments Selectively Suppressed the Viability of PC Cells by Reducing SMYD2 Expression but Did Not Adversely Affect the Non-Tumorigenic RWPE-1 Prostatic Epithelial Cells’ Viability at Therapeutic Doses
3.7. OC Treatments Suppressed the Migration and Invasion of the CRPC CWR-R1ca Cells
3.8. OC Treatments Inhibited the Colony Formation of the Wild but Not the SMYD2-KO CWR-R1ca Cells
3.9. Oral OC-PF Treatments Suppressed the Progression of CWR-R1ca-Luc Cells Engrafted into Nude Mice
3.10. Immunofluorsence Expression Comparison of ki67 and CD31 in OC Versus Placebo Control Treatments in Collected mCRPC Primary Tumors
3.11. OC Treatments Reduced the Expression of SMYD2 and Downstream Signals in Collected mCRPC Primary Tumors
3.12. Oleocanthal PF Treatment Inhibited Locoregional Recurrence of the mCRPC CWR-R1ca Cells in Nude Mice after Primary Tumor Surgical Excision
3.13. In Vivo Safety of OC-PF Treatments
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cell Line | Oleocanthal | Paclitaxel | Docetaxel | Enzalutamide | Cisplatin | |
---|---|---|---|---|---|---|
IC50 µM | IC50 nM | IC50 nM | IC50 µM | IC50 µM | ||
(24 h) | (48 h) | (48 h) | (48 h) | (48 h) | (48 h) | |
CWR-R1ca | 3.59 | 1.08 | 4.9 | 2.2 | 84.2 | 24.3 |
PC-3 | 0.64 | 0.58 | 6.6 | 2.0 | 70.1 | 6.1 |
PC-3M | 1.03 | 0.80 | 3.7 | 2.8 | 90.1 | 50.8 |
DU-145 | 5.35 | 3.32 | 5.7 | 2.6 | 47.0 | 15.3 |
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Siddique, A.B.; Ebrahim, H.Y.; Tajmim, A.; King, J.A.; Abdelwahed, K.S.; Abd Elmageed, Z.Y.; El Sayed, K.A. Oleocanthal Attenuates Metastatic Castration-Resistant Prostate Cancer Progression and Recurrence by Targeting SMYD2. Cancers 2022, 14, 3542. https://doi.org/10.3390/cancers14143542
Siddique AB, Ebrahim HY, Tajmim A, King JA, Abdelwahed KS, Abd Elmageed ZY, El Sayed KA. Oleocanthal Attenuates Metastatic Castration-Resistant Prostate Cancer Progression and Recurrence by Targeting SMYD2. Cancers. 2022; 14(14):3542. https://doi.org/10.3390/cancers14143542
Chicago/Turabian StyleSiddique, Abu Bakar, Hassan Y. Ebrahim, Afsana Tajmim, Judy Ann King, Khaldoun S. Abdelwahed, Zakaria Y. Abd Elmageed, and Khalid A. El Sayed. 2022. "Oleocanthal Attenuates Metastatic Castration-Resistant Prostate Cancer Progression and Recurrence by Targeting SMYD2" Cancers 14, no. 14: 3542. https://doi.org/10.3390/cancers14143542