Anti-Breast Cancer Properties and In Vivo Safety Profile of a Bis-Carbazole Derivative
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Cultures
2.2. Cell Viability
2.3. TUNEL Assay
2.4. Caspases Assay
2.5. Immunofluorescence Studies and Mitochondria Staining
2.6. In Vitro Tubulin Polymerization Assay
2.7. Molecular Docking
2.8. In Vivo Studies
2.9. Hydrolytic Stability Test
2.10. Statistical Analysis
3. Results and Discussion
3.1. Anticancer Activity and DNA Damage
3.2. Compound 1 Treatment Induces MDA-MB-231 Breast Cancer Cells Apoptosis
3.3. Docking Studies
3.4. Compound 1 Interferes with MDA-MB-231 Cells Cytoskeleton Dynamics
3.5. In Vivo Studies
3.6. Compound 1 Stability
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
MTAs | microtubule-targeting agents |
MTT | 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium Bromide |
DMSO | dimethyl sulfoxide |
TUNEL | terminal deoxynucleotidyl transferase dUTP nick end labeling |
DAPI | 4′,6-diamidino-2-phenylindole |
SD | standard deviations |
RMSD | root mean square deviation |
AST | aspartate transaminase |
ALT | alanine transaminase |
ALP | alkaline phosphatase |
RBC | red blood cell |
HB | hemoglobin |
HCT | hematocrit |
MCH | mean corpuscular hemoglobin |
WBC | white blood cell |
MCV | mean corpuscular volume |
MCHC | mean corpuscular hemoglobin concentration |
PLT | platelet |
WBC | white blood cells |
LYM | lymphocytes |
NEU | neutrophils |
EOS | eosinophils |
MAC | macrophages |
BASO | basophile |
OD | optical density |
NC | negative control |
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IC50 (µM) | SI | ||||
---|---|---|---|---|---|
MCF-7 | MDA-MB-231 | MCF-10A | MCF-7 | MDA-MB-231 | |
Compound 1 | 0.6 ± 0.3 | 0.3 ± 0.2 | >100 | >166.7 | >333.3 |
Ellipticine | 1.3 ± 0.2 | 1.9 ± 0.1 | 1.2 ± 0.3 | 0.9 | 0.8 |
Vinblastine | (36.8 ± 0.7) × 10−3 | (130.2 ± 1.1) × 10−3 | (17.2 ± 0.6) × 10−3 | 0.13 | 0.47 |
Paclitaxel | (1.3 ± 0.7) × 10−2 | (1.9 ± 0.5) × 10−2 | (6.4 ± 0.8) × 10−1 | 33.7 | 49.2 |
Organ Coefficient (mg/10 g) = 10 × Body Weight/Weight of the Mouse | ||||||
---|---|---|---|---|---|---|
Spleen | Liver | Lung | Brain | Heart | Kidney | |
NC | 0.056 ± 0.019 | 0.48 ± 0.047 | 0.08 ± 0.018 | 0.133 ± 0.025 | 0.057 ± 0.007 | 0.069 ± 0.006 |
1 | 0.07 ± 0.02 | 0.54 ± 0.03 | 0.11 ± 0.01 | 0.13 ± 0.03 | 0.06 ± 0.01 | 0.07 ± 0.01 |
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Ceramella, J.; Rosano, C.; Iacopetta, D.; Ben Toumia, I.; Chekir-Ghedira, L.; Maatouk, M.; Mariconda, A.; Longo, P.; Dallemagne, P.; Rochais, C.; et al. Anti-Breast Cancer Properties and In Vivo Safety Profile of a Bis-Carbazole Derivative. Pharmaceutics 2025, 17, 415. https://doi.org/10.3390/pharmaceutics17040415
Ceramella J, Rosano C, Iacopetta D, Ben Toumia I, Chekir-Ghedira L, Maatouk M, Mariconda A, Longo P, Dallemagne P, Rochais C, et al. Anti-Breast Cancer Properties and In Vivo Safety Profile of a Bis-Carbazole Derivative. Pharmaceutics. 2025; 17(4):415. https://doi.org/10.3390/pharmaceutics17040415
Chicago/Turabian StyleCeramella, Jessica, Camillo Rosano, Domenico Iacopetta, Iméne Ben Toumia, Leila Chekir-Ghedira, Mouna Maatouk, Annaluisa Mariconda, Pasquale Longo, Patrick Dallemagne, Christophe Rochais, and et al. 2025. "Anti-Breast Cancer Properties and In Vivo Safety Profile of a Bis-Carbazole Derivative" Pharmaceutics 17, no. 4: 415. https://doi.org/10.3390/pharmaceutics17040415
APA StyleCeramella, J., Rosano, C., Iacopetta, D., Ben Toumia, I., Chekir-Ghedira, L., Maatouk, M., Mariconda, A., Longo, P., Dallemagne, P., Rochais, C., & Sinicropi, M. S. (2025). Anti-Breast Cancer Properties and In Vivo Safety Profile of a Bis-Carbazole Derivative. Pharmaceutics, 17(4), 415. https://doi.org/10.3390/pharmaceutics17040415