Interaction of Artepillin C with model membranes: Effects of pH and ionic strength

Author(s)

Pazin, Wallance Moreira ^[1] ; Marques Ruiz, Gilia Cristine ^[1] ; de Oliveira, Jr., Osvaldo Novais ^[2] ; Leopoldo Constantino, Carlos Jose ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Sci & Technol, Dept Phys, Presidente Prudente, SP - Brazil

^[2] Univ Sao Paulo, Sao Carlos Inst Phys, Sao Carlos, SP - Brazil

• Document type: Journal article
• Source: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES; v. 1861, n. 2, p. 410-417, FEB 1 2019.
• Web of Science Citations: 3

Abstract

Artepillin C is the major constituent of green propolis, one of the most consumed products in popular medicine owing to its therapeutic effects, including antitumor activity. Artepillin C differs from other cinnamic acid derivatives due to the presence of two prenylated groups in its structure, believed to enhance access to the cell membrane and resulting in pharmacological activity. The membrane outer leaflet of tumor cells is exposed to an acidic extracellular environment, which could modulate the protonation state of antitumor drugs and hence their interaction with the cell membrane. Herein, we investigated the interaction of Artepillin C with Langmuir monolayers and giant unilamellar vesicles (GUVs) of 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) used as model membranes, in physiological and acidic environments. We observed that protonation of the carboxyl group of Artepillin C is essential for the interaction, with larger shifts induced in the surface pressure isotherms of DPPC monolayers in comparison with deprotonated Artepillin C. Also observed was a decrease in lipid packing inferred from the compressibility modulus and Brewster angle microscopy (BAM) images for monolayers on acidic subphases. Results with microscopy techniques on GUVs confirmed that. Artepillin C causes a curvature stress of the lipid bilayer only in its neutral state, causing the GUVs to burst. The stronger effects of neutral Artepillin C on both monolayers and GUVs were maintained when the ionic strength was increased. Taken together, the results indicate that Artepillin C may have preferential attachment to a more acidic environment which might be an important feature for its antitumor activity. (AU)

• FAPESP's process: 13/14262-7 - Nanostructured films from biologically-relevant materials
• Grantee: Osvaldo Novais de Oliveira Junior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/09633-4 - Mechanism of action of the bioactive compound Artepillin C in membrane biomimetic systems and cytoplasmic membrane of tumor cells
• Grantee: Wallance Moreira Pazin
• Support Opportunities: Scholarships in Brazil - Post-Doctoral