Changes in electric charge and phospholipids composition in human colorectal cancer cells.
ABSTRACT Cancer cells perform their malicious activities through own cell membranes that screen and transmit inhibitory and stimulatory signals out of the cells and into them. This work is focused on changes of phospholipids content (PI-phosphatidylinositol, PS-phosphatidylserine, PE-phosphatidylethanolamine, PC-phosphatidylcholine) and electric charge that occur in cell membranes of colorectal cancer of pT 3 stage, various grades (G2, G3) and without/with metastasis. Qualitative and quantitative composition of phospholipids in the membrane was determined by HPLC (high-performance liquid chromatography). The surface charge density of colorectal cancer cell membranes was measured using electrophoresis. The measurements were carried out at various pH of solution. It was shown that the process of cancer transformation was accompanied by an increase in total amount of phospholipids as well as an increase in total positive charge at low pH and total negative charge at high pH. A malignant neoplasm cells with metastases are characterized by a higher PC/PE ratio than malignant neoplasm cells without metastases.
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ABSTRACT: Cancer is a leading cause of death worldwide and conventional chemotherapeutic treatments are not always effective, induce resistance and are often associated with serious side effects. Cationic antimicrobial peptides (AMPs) represent a promising alternative to conventional anticancer drugs due to their selectivity for malignant cells and their non-toxic properties. One such class of peptides is cecropins, initially identified in insects but later isolated also from mammalian tissues. Although electrostatic attraction between the negatively charged cancer cells and the positively charged AMPs is believed to play a major role in the strong binding and selective disruption of bacterial and cancer cell membranes, the exact mechanism of action has not been elucidated yet. Using these peptides as therapeutic agents requires a detailed understanding of their mechanisms of action. Our goal is to better understand the interaction between cecropin P and membrane using molecular dynamics simulations (20ns simulation time) of atomically detailed models of cecropin P in interaction with POPE lipid bilayer. We built three different systems, in which the cecropin helix is initially oriented parallel with the lipid bilayer. In the first two systems electrostatic interactions are favoured, since peptide helix is oriented with positive charges facing negatively charged lipid phosphate groups and the distance between helix axis and phosphate plane is 9A and 6A, respectively. In the third system, hydrophobic interactions are favoured, cecropin helix is partially buried in the membrane bilayer, with the apolar side interacting with hydrophobic lipid tails and the cationic face interacting with phosphate groups. Our results indicate a lower stability of the first two systems, based on electrostatic interactions, while the system in which hydrophobic interactions dominate is highly stable and peptide induces deformations of the lipid bilayer. These results suggest that the hydrophobic characteristics of the peptide may be used to facilitate peptide penetration in the membrane.
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ABSTRACT: Developing nanomaterials that are effective, safe, and selective for gene transfer applications is challenging. Bacteriophages (phage), viruses that infect bacteria only, have shown promise for targeted gene transfer applications. Unfortunately, limited progress has been achieved in improving their potential to overcome mammalian cellular barriers. We hypothesized that chemical modification of the bacteriophage capsid could be applied to improve targeted gene delivery by phage vectors into mammalian cells. Here, we introduce a novel hybrid system consisting of two classes of nanomaterial systems, cationic polymers and M13 bacteriophage virus particles genetically engineered to display a tumor-targeting ligand and carry a transgene cassette. We demonstrate that the phage complex with cationic polymers generates positively charged phage and large aggregates that show enhanced cell surface attachment, buffering capacity, and improved transgene expression while retaining cell type specificity. Moreover, phage/polymer complexes carrying a therapeutic gene achieve greater cancer cell killing than phage alone. This new class of hybrid nanomaterial platform can advance targeted gene delivery applications by bacteriophage.Molecular therapy. Nucleic acids. 08/2014; 3:e185.
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ABSTRACT: Abstract Bioactive peptides are specific protein fragments that have positive impact on health. They are important sources of new biomedicine, energy and high-performance materials. The beneficial effects of bioactive peptides are due to their antioxidant, antihypertensive, anticarcinogenic, antimicrobial, and immunomodulatory activities. The structure-activity relationship of bioactive peptides plays a significant role in the development of innovative and unconventional synthetic polymeric counterparts. It provides the basis of the stereospecific synthesis, transformation, and development of bioactive peptide products. This review covers the progress of studies in the structure-activity relationship of some bioactive peptides including antioxidant peptides, angiotensin-I-converting enzyme-inhibitory peptides, and anticarcinogenic peptides in the past decade.Journal of medicinal food. 08/2014;