Insights on the interaction of Artepillin C with tumor cell membranes: an advanced fluorescence microscopy study

Abstract

Artepillin C is the major constituent of green propolis, one of the most consumed products in folk medicine. It has been reported that Artepillin C displays, among several therapeutic effects, antitumor activity, especially due to the presence of two prenylated groups in its structure, believed to enhance access to the cell membrane. However, membrane outer leaflet of tumor cells is exposed to an acidic extracellular environment, which could modulate the protonation state of antitumor drugs and, consequently, its interaction for cell membrane. Previous study has been performed within the postdoctoral project (FAPESP number 2016/09633-4), evidencing that Artepillin C in an acidic environment, as in the case of extracellular matrix of tumor cells, has potential to alter and damage lipid packing. The next step of this project, to be developed within Dr. Jonathan Brewer's group, at University of Southern Denmark, is to obtain a complete understanding of antitumor activity of Artepillin C by taking into account the cell membrane complexity of tumor cells. Brewer and his group have published relevant papers in the broad field of biological systems and their interactions with bioactive compounds, especially by using microscopy techniques, which are able to investigate dynamical and morphological properties of cell membranes. We highlight the Stimulated Emission Depletion (STED) microscopy, a super resolution fluorescence technique available at Brewer's laboratory that has been greatly used as an advanced bioimaging technique to answer fundamental questions in biological systems. The collaboration with Brewer's group will be important for the progress of our research regarding the mechanism of action of Artepillin C on plasma membrane of tumor cell, associating such effects to the previous study with model membranes performed as part of this research.