LyeTx I-b Peptide Attenuates Tumor Burden and Metastasis in a Mouse 4T1 Breast Cancer Model
Abstract
:1. Introduction
2. Results
2.1. LyeTx I-b Peptide Shows Cytotoxicity against Human and Mouse Breast Cancer Cells
2.2. LyeTxI-b Peptide Reduces the Clonogenic Survival of 4T1 Cells
2.3. LyeTxI-b Increases Sub-Diploid DNA Content and Exposure to Phosphatidylserine
2.4. Sub-Acute Toxicity of LyeTx I-b Peptide
2.5. Intratumoral Administration of LyeTxI-b Decreases Tumor Growth and Lung Metastatic Nodules
2.6. Systemic Subcutaneous Injection of LyeTx I-b Reduces Tumor Volume
2.7. Systemic Subcutaneous Injection of LyeTx I-b Peptide Reduces Neoplastic Cells in Primary Tumor
2.8. No Liver Function Alteration Was Induced by LyeTx I-b Treatment
2.9. LyeTx I-b and Carboplatin Reduce the Total and Differential Leukocyte Counts
2.10. LyeTx I-b Alters the Numbers of Rolling and Adhering Leukocytes
2.11. LyeTx I-b Decreases the Level of Cytokines in the Tumor Microenvironment
3. Discussion
4. Materials and Methods
4.1. Cell Lines
4.2. Evaluation of Cell Viability Using the MTT Assay
4.3. Cell Cycle Analysis
4.4. Quantitation of Cell Death Using Annexin V and PI
4.5. Evaluation of the Clonogenic Survival of 4T1 Cells after the Treatment with LyeTx I-b
4.6. Animals and Procedures
4.7. Sub-Acute Toxicity of LyeTx I-b Peptide In Vivo
4.8. Tumor Inoculation and Drug Treatment
4.9. Intratumoral Drug Administration
4.10. Subcutaneous Cells and Drug Administration
4.11. Histological Analysis
4.12. Evaluation of Liver Integrity
4.13. Complete Blood Count
4.14. Manual Quantification of Differential Leukocytes
4.15. Detection and Quantitation of Cytokines and Growth Factors
4.16. Intravital Microscopy
4.17. Statistical Analyses
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cell Line | LyeTx I-b IC50 (µM) | Carboplatin IC50 (µM) |
---|---|---|
4T1 | 6.5 ± 5.30 | ≥100 |
MCF-7 | 7.34 ± 3.09 | ≥100 |
MDA-MB-231 | 5.77 ± 0.83 | 69.20 ± 1.22 |
The IC50 values were calculated based on the linear regression of the dose-log response curves after 48 h exposure to the peptide or carboplatin, determined by the MTT and resazurin assays. The values represent the mean ± S.D. of at least 3 independent experiments. Representative concentration-response curves are displayed below. | ||
|
Hematological Parameter | Control | LyeTx I_b Peptide |
---|---|---|
RBC (×106/mm3) | 6.32 ± 0.667 | 7.46 ± 0.965 |
Hb (g/dL) | 10.8 ± 2.66 | 12.9 ± 0.680 |
Hematocrit | 38.9 ± 8.66 | 39.4 ± 2.56 |
MCV (fL) | 61 ± 7.57 | 48 ± 4.50 |
MCH (Pg) | 16.7 ± 0.458 | 16.0 ± 0.11 |
MCHC % | 28.5 ± 3.06 | 31.6 ± 1.34 |
WBC (×103/mm3) | 2.3 ± 2.26 | 4.1 ± 0.70 |
Lymphocytes | 91.7 ± 5.13 | 89.2 ± 4.03 |
Monocytes | 4.3 ± 1.556 | 4.1 ± 1.553 |
Neutrophils | 4 ± 3.59 | 6.7 ± 2.66 |
Platelets (×103/mm3) | 443 ± 73.6 | 278 ± 80.0 * |
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Abdel-Salam, M.A.L.; Pinto, B.; Cassali, G.; Bueno, L.; Pêgas, G.; Oliveira, F.; Silva, I.; Klein, A.; Souza-Fagundes, E.M.d.; de Lima, M.E.; et al. LyeTx I-b Peptide Attenuates Tumor Burden and Metastasis in a Mouse 4T1 Breast Cancer Model. Antibiotics 2021, 10, 1136. https://doi.org/10.3390/antibiotics10091136
Abdel-Salam MAL, Pinto B, Cassali G, Bueno L, Pêgas G, Oliveira F, Silva I, Klein A, Souza-Fagundes EMd, de Lima ME, et al. LyeTx I-b Peptide Attenuates Tumor Burden and Metastasis in a Mouse 4T1 Breast Cancer Model. Antibiotics. 2021; 10(9):1136. https://doi.org/10.3390/antibiotics10091136
Chicago/Turabian StyleAbdel-Salam, Mostafa A. L., Bárbara Pinto, Geovanni Cassali, Lilian Bueno, Gabriela Pêgas, Fabrício Oliveira, Irismara Silva, André Klein, Elaine Maria de Souza-Fagundes, Maria Elena de Lima, and et al. 2021. "LyeTx I-b Peptide Attenuates Tumor Burden and Metastasis in a Mouse 4T1 Breast Cancer Model" Antibiotics 10, no. 9: 1136. https://doi.org/10.3390/antibiotics10091136