Membrane lipid composition is associated with differential sensitivity to apigenin in U937 and HL-60 cells: insights from cell-based and Langmuir monolayer studies

Apigenin is a naturally occurring dietary flavonoid increasingly investigated for its biological activity, including effects on cell survival, oxidative stress, and membrane-associated processes. Interactions between polyphenols and membrane lipids may influence membrane organization and contribute to differences in cellular responses. This study examined the effects of apigenin on human myeloid U937 and HL-60 cells using an integrated approach combining biological assays with biomimetic membrane models. Cell viability and oxidative stress-related parameters were evaluated using MTT, LDH, and MDA assays. In parallel, Langmuir lipid monolayers reproducing the characteristic membrane lipid compositions of U937 and HL-60 cells were used to investigate the effects of apigenin on membrane mechanical properties. Apigenin reduced cell viability in a concentration-dependent manner, with HL-60 cells exhibiting greater sensitivity than U937 cells. Biophysical analyses showed that apigenin altered lipid monolayer properties by decreasing the compression modulus and increasing membrane elasticity. The magnitude of these effects depended on membrane lipid composition and was more pronounced in HL-60 membrane models, paralleling the greater sensitivity observed in cellular assays. These findings demonstrate that membrane lipid composition may contribute to variations in cellular sensitivity to apigenin and highlight the importance of membrane organization in studies of lipid-polyphenol interactions and their biological consequences.