INTERACTION OF THE ANTITUMORIGENIC COMPOUND ANASTROZOLE IN CELL MEMBRANE MODELS USING LANGMUIR MONOLAYERS

Many interactions of bioactive compounds, like anticancer drugs, in cell membranes present a molecular mechanism of action not completely elucidated yet. For this reason, it is essential to study the interaction of these compounds in simplified models of cell membranes, such as Langmuir monolayers. This kind of structure is formed when insoluble amphiphiles are first dissolved in organic solvents and then spread on the air-water interface, forming a monomolecular film. In this work, we studied an antitumorigenic compound, anastrozole, in cell membrane models formed by Langmuir monolayer of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), a known lipid for mimic erythrocytes membranes to evaluate first the toxicity in healthy cells. For that, we co-spread the compound and the lipid on the air-water interface and characterized the assembled monolayer with tensiometric measurements, morphological (Brewster Angle Microscopy), electric (surface potential), and rheological measurements (oscillating barriers). Surface pressure-area isotherms showed that anastrozole shifted the isotherm of DPPC to higher areas, indicating the expansion of the monolayer due to its penetration into the film; it also decreased the surface potential due to tilting of the lipid alkyl chains during the penetration. The drug stabilized the previously compressed monolayers up to 30 mN/m and did not cause the formation of significant interfacial aggregates. Compression-decompression curves did not present hysteresis for the pure and the mixed monolayer, confirming that anastrozole may not induce the formation of interfacial aggregates. Rheological measurements showed that the compound decreased the viscoelastic modulus for the DPPC monolayer, making the film more fluid but keeping it in the liquid-condensed state. Also, no additional viscous contributions were observed upon incorporation of anastrozole. These results show that this antitumorigenic compound interacts with cell membrane models but with no abrupt changes in the molecular structure and thermodynamic properties, discarding possible toxicity in models of erythrocyte cells, which is essential to understand the mechanism of action of anticancer drugs at the molecular level.

This work was supported by FAPESP (2022/03736-7) and CNPq.