Myconoside interacts with the plasma membranes and the actin cytoskeleton and provokes cytotoxicity in human lung adenocarcinoma A549 cells.

Studies have been carried out on the effects of the phenyl glycoside myconoside, extracted from the relict, Balkan endemic resurrection plant Haberlea rhodopensis on the plasma membrane structural organization and the actin cytoskeleton. Because the plasma membrane is the first target of exogenous bioactive compounds, we focused our attention on the influence of myconoside on the membrane lipid order and actin cytoskeleton in human lung adenocarcinoma A549 cells, using fluorescent spectroscopy and microscopy techniques. We found that low myconoside concentration (5 μg/ml) did not change cell viability but was able to increase plasma membrane lipid order of the treated cells. Higher myconoside concentration (20 μg/ml) inhibited cell viability by decreasing plasma membrane lipid order and impairing actin cytoskeleton. We hypothesize that the observed changes in the plasma membrane structural organization and the actin cytoskeleton are functionally connected to cell viability. Biomimetic membranes were used to demonstrate that myconoside is able to reorganize the membrane lipids by changing the fraction of sphingomyelin-cholesterol enriched domains. Thus, we propose a putative mechanism of action of myconoside on A549 cells plasma membrane lipids as well as on actin filaments in order to explain its cytotoxic effect at high myconoside concentration.