Molecularly Engineered Surfactin Analogues Induce Nonapoptotic-Like Cell Death and Increased Selectivity in Multiple
Rebecca T Miceli1, Filbert Totsingan1, Tasnim Naina1
1Center for Biotechnology and Interdisciplinary Sciences, Department of Chemistry and Chemical Biology, Department of Biomedical Engineering, Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York 12180, United States.
ACS Omega
|May 1, 2023
Summary
Modifying surfactin, a biosurfactant from Bacillus subtilis, altered its properties. Amplified anionic charge enhanced breast cancer cell activity while sparing normal cells, suggesting potential for targeted therapies.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Surfactin is a lipopeptide biosurfactant produced by Bacillus subtilis.
- Its structure comprises a cyclic heptapeptide and a fatty acid chain.
- Understanding surfactin's structure-activity relationship is crucial for therapeutic development.
Purpose of the Study:
- To investigate how modifications to surfactin's molecular skeleton affect its activity and selectivity against breast cancer.
- To synthesize and characterize novel surfactin derivatives.
- To correlate physicochemical properties with biological activity.
Main Methods:
- Six synthetic surfactin analogs were generated by conjugating amine-functionalized molecules to carboxyl groups.
- Purification and structural analysis of synthetic surfactins.
- Dose-dependent growth inhibition assays on breast cancer cell lines (monolayer and spheroid), fibroblasts, and erythrocytes.
- Determination of selectivity indices.
- Correlation analysis between physicochemical properties (e.g., critical micelle concentration) and biological activity.
Main Results:
- Two surfactin derivatives with increased anionic charge demonstrated enhanced activity against breast cancer cells and reduced activity against normal cells.
- A cationic surfactin derivative showed increased activity across all tested cell lines.
- A significant correlation was found between critical micelle concentration and activity against multiple cell lines.
Conclusions:
- Modification of surfactin's molecular skeleton can modulate its anticancer activity and selectivity.
- Anionic surfactin derivatives show promise for targeted breast cancer therapy.
- Physicochemical properties, particularly critical micelle concentration, are key determinants of surfactin's biological activity.
