Location and Effects of an Antitumoral Catechin on the Structural Properties of Phosphatidylethanolamine Membranes

Abstract

Green tea catechins exhibit high diversity of biological effects including antioncogenic properties, and there is enormous interest in their potential use in the treatment of a number of pathologies. It is recognized that the mechanism underlying the activity of catechins relay in part in processes related to the membrane, and many studies revealed that the ability of catechins to interact with lipids plays a probably necessary role in their mechanism of action. We present in this work the characterization of the interaction between an antitumoral synthetically modified catechin (3-O-(3,4,5-trimethoxybenzoyl)-(´)-catechin, TMCG) and dimiristoylphosphatidyl-ethanolamine (DMPE) membranes using an array of biophysical techniques which include differential scanning calorimetry, X-ray diffraction, infrared spectroscopy, atomic force microscopy, and molecular dynamics simulations. We found that TMCG incorporate into DMPE bilayers perturbing the thermotropic transition from the gel to the fluid state forming enriched domains which separated into different gel phases. TMCG does not influence the overall bilayer assembly of phosphatidylethanolamine systems but it manages to influence the interfacial region of the membrane and slightly decrease the interlamellar repeat distance of the bilayer. TMCG seems to be located in the interior of the phosphatidylethanolamine bilayer with the methoxy groups being in the deepest position and some portion of the molecule interacting with the water interface. We believe that the reported interactions are significant not only from the point of view of the known antitumoral effect of TMCG, but also might contribute to understanding the basic molecular mechanism of the biological effects of the catechins found at the membrane level.

Plant Polyphenols as Antioxidant and Antibacterial Agents for Shelf‐Life Extension of Meat and Meat Products: Classification, Structures, Sources, and Action Mechanisms

“…Because of their antioxidant and antimicrobial properties, commercially available polyphenols and plant extracts rich in polyphenols might be useful for preserving meat/meat products from oxidative deterioration, bacterial spoilage, and the growth of pathogens. In the last decade, it has been shown that plant polyphenols have a positive impact on human health, reduce oxidative processes, inhibit growth of many pathogens [such as bacteria (Nakayama and others ; Song and others ), viruses (Shin and Chung ; Kohda and others ; Nantz and others ), and fungi (Park and others )], stimulate the growth of commensal and beneficial bacteria (Cardona and others ; Duda‐Chodak and others ; Mills and others ), and prevent chronic diseases (Yang and Hong ), including cancer (Casado and others ). For these reasons, polyphenols are increasingly being used in the meat industry as an alternative to chemical antioxidants and antimicrobials.…”

Effects of a Semisynthetic Catechin on Phosphatidylglycerol Membranes: A Mixed Experimental and Simulation Study

“…Additionally, a new peak emerged at a fixed temperature, near 8 °C, when TMBC reached 0.20 mole fraction. The appearance of a transition peak at a lower and fixed temperature has also been detected in zwitterionic bilayers containing elevated concentrations of TMBC [ 42 , 43 ].…”

“…The temperature of the fluidus line remained constant in the whole range of TMBC concentrations which suggests that an immiscibility in the liquid-crystalline phase was present. The TMBC-induced fluid-phase immiscibility has not been observed in mixtures of TMBC with any other glycerophospholipids with different polar head groups [ 42 , 43 , 44 ]. The DMPG system evolves from a gel phase, which shows immiscibility from a certain catechin concentration, to an immiscible fluid phase through a coexistence region which is wider as more TMBC is present in the bilayer.…”

“…TMBC ( Figure 1 ) is a structural analog of catechin that has been shown to exert high antiproliferative activity against melanoma and breast cancer cells [ 40 , 41 ]. It has been shown that TMBC perturbs the structural properties of the bilayers composed of phospholipids bearing different polar head groups, including phosphatidylcholine [ 42 ], phosphatidylethanolamine [ 43 ], and phosphatidylserine [ 44 ]. In this work, in order to advance the knowledge of the molecular interaction between catechins and individual membrane phospholipid species, we present a study on the effect of TMBC on the structural and dynamic properties of biomimetic model systems composed of 1,2-dimyristoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DMPG), by using differential scanning calorimetry (DSC), X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, and molecular dynamics simulation.…”