Back to Search
Start Over
In vitro and in vivo activity of a novel oxamide-hydrazone hybrid derivative against triple-negative breast cancer.
- Source :
-
Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Jul; Vol. 397 (7), pp. 5119-5129. Date of Electronic Publication: 2024 Jan 19. - Publication Year :
- 2024
-
Abstract
- Triple-negative breast cancer is a subtype of breast cancer with poor clinical outcome, and currently, no effective targeted therapies are available. Since cancer develops owing to deregulation of apoptosis, employing therapeutic strategies with the ability to target the molecules involved in apoptosis induction would provide a valid approach to hinder tumor progression. Hydrazide-hydrazones and oxamide molecules are the subject of intense studies due to their anticancer effects via apoptosis induction. In the present study, we attempted to elucidate the mechanism of action of a synthesized compound (compound A) in inducing cell death. Annexin/PI and Western blotting analyses, DAPI staining, mitochondrial membrane potential probe, and flow cytometry were applied for the in vitro evaluations. 4T1 syngeneic mouse model and immunohistochemistry were used for the in vivo assessments. Compound A caused cell death by inducing apoptosis in MDA-MB-231 cells in a mitochondrial-dependent manner at high concentrations after 72 h of incubation. Compound A also impeded tumor growth in a 4T1 syngeneic mouse model as evidenced by hematoxylin and eosin staining of the tumors. Furthermore, it significantly diminished the expression of pro-caspase-3, Ki67, and CD31 markers in the tumor sections. Conclusively, this study for the first time reports the anti-cancer efficacy of compound A in both in vitro and in vivo models and its potential in the treatment of triple-negative breast cancer.<br /> (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Subjects :
- Animals
Female
Cell Line, Tumor
Humans
Mice
Membrane Potential, Mitochondrial drug effects
Ki-67 Antigen metabolism
Platelet Endothelial Cell Adhesion Molecule-1 metabolism
Triple Negative Breast Neoplasms drug therapy
Triple Negative Breast Neoplasms pathology
Hydrazones pharmacology
Hydrazones chemical synthesis
Hydrazones therapeutic use
Apoptosis drug effects
Antineoplastic Agents pharmacology
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Mice, Inbred BALB C
Subjects
Details
- Language :
- English
- ISSN :
- 1432-1912
- Volume :
- 397
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Naunyn-Schmiedeberg's archives of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38240779
- Full Text :
- https://doi.org/10.1007/s00210-023-02931-6