Amphotericin-A21 Induces Antineoplastic Effects through the Modulation of Apoptosis in Human Tumoral Cells
Lourdes Rodríguez-Fragoso1, Rubi Escobar-Reséndiz1, Arturo Galván-Hernández2
1Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Mexico.
Introduction:
While the high morbidity of cancer continues to affect the global population, there are currently no effective and safe therapeutic options. Amphotericin-A21 (AmB-A21) is a derivative of amphotericin B (AmB). Its efficacy is similar to that of its precursor, but it has greater safety. AmB-A21 can induce apoptosis in neoplastic cells, meaning it could potentially be employed as a safe chemotherapeutic agent.
Methods:
This study examined the antineoplastic effect of AmB-A21 on MCF-7, U-87MG, and A-549 cells by evaluating cytotoxicity, apoptosis, and protein expressions associated with cell death. MCF-7 cells were treated with AmB-A21 at 40 µ
Results:
AmB-A21 reduced cell viability in a time-dependent manner. At 72 h, cell viability was reduced by 67% in MCF-7, 48% in U-87MG, and 47% in A-549 cells. AmB-A21 induced apoptosis by 50%, 58%, and 80% in MCF-7, U-87MG, and A-549 cells, respectively. A significant reduction in Bcl-2 expression and an important increase in Bax expression (55%/2.8-fold in MCF-7 cells, 40%/3.5 fold in U-87MG cells, and 45%/4.5-fold in A-549 cells) were also observed. AmB-A21 likewise increased caspase 9 activity 8.5-fold in MCF-7 cells, 4.1-fold in U-87MG cells, and 8-fold in A-549 cells.
Conclusion:
Although comparatively AmB-A21 concentration for U-87MG cells was higher, it has potential for cancer therapy due to its safer profile.
Insights
Amphotericin-A21 (AmB-A21) demonstrates significant anticancer effects by inducing apoptosis and reducing cell viability in various cancer cell lines. This derivative of amphotericin B (AmB) shows promise as a safer chemotherapeutic agent.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Cancer remains a significant global health challenge with limited effective and safe therapeutic options.
- Amphotericin-A21 (AmB-A21), a derivative of amphotericin B (AmB), offers comparable efficacy to AmB but with an improved safety profile.
- AmB-A21 exhibits the ability to induce apoptosis in neoplastic cells, positioning it as a potential chemotherapeutic agent.
Purpose of the Study:
- To investigate the antineoplastic effects of AmB-A21 on human cancer cell lines.
- To evaluate the impact of AmB-A21 on cell viability, apoptosis induction, and key protein expressions related to cell death.
- To compare the efficacy of AmB-A21 with AmB and cisplatin.
Main Methods:
- MCF-7, U-87MG, and A-549 cancer cells were treated with specific concentrations of AmB-A21.
- Cytotoxicity, apoptosis, and protein expression levels (Bcl-2, Bax) were assessed.
- Caspase 9 activity was measured to evaluate the apoptotic pathway.
- Comparative analyses were performed using AmB and cisplatin as controls.
Main Results:
- AmB-A21 significantly reduced cancer cell viability in a time-dependent manner across all tested cell lines.
- The compound effectively induced apoptosis, with notable increases in Bax expression and reductions in Bcl-2 expression.
- AmB-A21 markedly increased caspase 9 activity, indicating activation of the intrinsic apoptotic pathway.
Conclusions:
- AmB-A21 exhibits potent antineoplastic activity against MCF-7, U-87MG, and A-549 cells.
- The observed induction of apoptosis and modulation of Bcl-2/Bax expression highlight AmB-A21's mechanism of action.
- Despite requiring a higher concentration for U-87MG cells, AmB-A21's favorable safety profile suggests its potential as a novel cancer therapeutic.
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