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Toxicity of amphotericin B and its methyl ester toward normal and tumor cell lines
Abstract:
The toxicity of amphotericin B, amphotericin B methyl ester (AME), and Fungizone toward three "normal" and three tumor-derived human and mouse cell lines was evaluated in monolayer culture. AME was less toxic than amphotericin B and Fungizone to all cell lines, but the sensitivity of the normal and tumor lines was different. The human (HEL-8 and WISH) and mouse (L-M) cells derived from normal tissue were more resistant to AME than the tumor-derived human (KB and HeLa) and mouse (RAG) cell as indicated by: (a) increased 24-hr survival, (b) increased 72-hr viability, and (c) growth rates at higher AME concentrations. In contrast, no pattern of differential sensitivity was observed with amphotericin B and Fungizone.
Insights
Amphotericin B methyl ester (AME) shows differential toxicity, being less toxic overall but more selectively toxic to tumor cells than amphotericin B and Fungizone.
Area of Science:
- Pharmacology
- Toxicology
- Cell Biology
Background:
- Amphotericin B and Fungizone are established antifungal agents with known toxicities.
- Understanding differential cell line sensitivity is crucial for therapeutic development.
Purpose of the Study:
- To evaluate the toxicity of amphotericin B, amphotericin B methyl ester (AME), and Fungizone.
- To compare the differential sensitivity of normal and tumor-derived human and mouse cell lines to these agents.
Main Methods:
- Monolayer cell culture of three normal and three tumor-derived human and mouse cell lines.
- Assessment of cell viability, survival rates, and growth at varying concentrations of the antifungal agents.
Main Results:
- Amphotericin B methyl ester (AME) exhibited lower toxicity compared to amphotericin B and Fungizone across all tested cell lines.
- Normal human (HEL-8, WISH) and mouse (L-M) cells demonstrated higher resistance to AME than tumor-derived human (KB, HeLa) and mouse (RAG) cells.
- Differential sensitivity patterns were not observed with amphotericin B and Fungizone.
Conclusions:
- Amphotericin B methyl ester (AME) presents a potentially more favorable toxicity profile.
- AME displays selective toxicity, with normal cells being more resistant than tumor cells, suggesting therapeutic potential.
- Further investigation into AME's differential effects could lead to improved antifungal therapies.
