Pinus mugo Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells
Abstract
:1. Introduction
2. Results
2.1. Essential Oils Dose-Dependently Inhibit STAT3 Tyrosine Phosphorylation in DU145 Cancer Cells
2.2. Essentials Oils Induce Cytotoxicity in DU145 Cells
2.3. Chemical Composition of Essential Oil from Pinus mugo
2.4. Essential Oil from Pinus mugo Modulates Constitutive STAT3 Signaling
2.5. Essential Oil from Pinus mugo Modulates IL6-Induced STAT3 Activation
2.6. Essential Oil from Pinus mugo Modulates STAT3 Activation, Increasing ROS Generation
2.7. PMEO Induces Apoptotic Death in DU145 Cells
2.8. PMEO Impairs DU145 Cell Migration
2.9. PMEO Acts Synergistically with Cisplatin and Enhances Chemosensitivity of DU145 Cells
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. Cell Culture
4.3. Essential Oil Dilution
4.4. GC-MS Analysis
4.5. Western Blot Analysis
4.6. RT-qPCR Analysis
4.7. Cell Viability Assay
4.8. Glutathione Content Quantification
4.9. Measurement of Intracellular Reactive Oxygen Species
4.10. Study of Apoptotic Hallmarks
- (a).
- Dual staining with Annexin V–FITC and propidium iodide
- (b).
- Caspase-3 and Poly (ADP-ribose) polymerase (PARP) cleavage
4.11. Wound Healing Assay
4.12. Pharmacological Synergism Studies
4.13. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Essential Oil Plant Name | Essential Oil Acronyms | pTyr705STAT3 Inhibition IC50 (μg/mL) | Anti-STAT3 Potency |
---|---|---|---|
Pinus mugo | PMEO | <50 | Strong |
Lavandula angustifoglia | LAEO | <50 | Strong |
Pinus sylvestris | PSEO | <50 | Strong |
Cupressus sempervirens | CSEO | <50 | Strong |
Hyssopus officinalis | HOEO | 50–100 | Medium |
Juniperus oxycedrus | JOEO | 50–100 | Medium |
Myrtus communis | MCEO | 50–100 | Medium |
Chamaemelum Nobile | CNEO | 50–100 | Medium |
Melissa officinalis | MOEO | 50–100 | Medium |
Eucalyptus globulus | EGEO | 50–100 | Medium |
Pimpinella anisum | PAEO | >100 | Weak |
Cananga odorata | COEO | >100 | Weak |
Components 1 | LRI 2 | LRI 3 | % 4 |
---|---|---|---|
α-Pinene | 1018 | 1021 | 12.52 |
β-Pinene | 1090 | 1099 | 7.63 |
δ-3-Carene | 1142 | 1146 | 10.75 |
Limonene | 1190 | 1198 | 10.95 |
β-Phellandrene | 1201 | 1204 | 6.98 |
o-Cymene | 1279 | 1287 | 2.14 |
α-Copaene | 1492 | 1489 | 0.92 |
β-Cubebene | 1528 | 1532 | 1.17 |
Linalool | 1545 | 1547 | 0.18 |
Bornyl acetate | 1466 | 1567 | 13.44 |
Crypton | 1672 | 1675 | 3.70 |
β-Caryophyllene | 1612 | 1619 | 21.41 |
Isopinocarveol | 1642 | 1646 | 0.47 |
α-Terpineol | 1650 | 1655 | 0.44 |
cis-Verbenol | 1665 | 1663 | 0.46 |
Humulene | 1669 | 1667 | 1.20 |
α-Muurolene | 1733 | 1729 | 1.08 |
δ-Cadinene | 1762 | 1758 | 1.61 |
Calamenene | 1835 | 1832 | 0.67 |
p-Cymen-8-ol | 1836 | 1838 | 0.85 |
trans-2-Caren-4-ol | 1844 | * | 0.59 |
Cumaldehyde | 1782 | 1781 | 0.55 |
SUM | 99.99 |
CI | DRI | ||
---|---|---|---|
Cisplatin | PMEO | ||
IC50 | 0.82 | 2.59 | 2.31 |
IC75 | 0.64 | 10.62 | 1.82 |
IC90 | 0.72 | 43.59 | 1.44 |
IC95 | 0.82 | 113.88 | 1.23 |
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Thalappil, M.A.; Butturini, E.; Carcereri de Prati, A.; Bettin, I.; Antonini, L.; Sapienza, F.U.; Garzoli, S.; Ragno, R.; Mariotto, S. Pinus mugo Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells. Molecules 2022, 27, 4834. https://doi.org/10.3390/molecules27154834
Thalappil MA, Butturini E, Carcereri de Prati A, Bettin I, Antonini L, Sapienza FU, Garzoli S, Ragno R, Mariotto S. Pinus mugo Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells. Molecules. 2022; 27(15):4834. https://doi.org/10.3390/molecules27154834
Chicago/Turabian StyleThalappil, Muhammed Ashiq, Elena Butturini, Alessandra Carcereri de Prati, Ilaria Bettin, Lorenzo Antonini, Filippo Umberto Sapienza, Stefania Garzoli, Rino Ragno, and Sofia Mariotto. 2022. "Pinus mugo Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells" Molecules 27, no. 15: 4834. https://doi.org/10.3390/molecules27154834