List of Publications by Department for the Academic Year Effect of Carboplatin on Phosphatidylcholine and Phosphatidylinositol Levels in the Plasma Membrane of Cancer Cells and Its Association with Invasiveness
Abstract
Background: Plasma membrane is the dynamic and complex structure of the cell that surrounds and protects the intracellular content. It is a lipid bilayer mainly composed of phospholipids. Their structural and functional properties are pivotal for the survival of the cell. Cancer cells perform their different activities through their cell membranes. These activities are reflected by alterations in the membrane lipids composition. Plasma membrane has been considered as a potential target for antitumor drugs. Carboplatin, a second-generation platinum analog of cisplatin with reduced side effects, was introduced into clinical trial in 1981. It is one of most widely used drugs in the treatment of several human solid tumors. Carboplatin binds with DNA to form intra-strand and inter-strand crosslinks that cause changes in the conformation of the DNA and affect DNA replication. Aim: We aimed in this study at examining the effect of carboplatin on phosphatidylcholine and phosphatidylinositol levels of the plasma membrane of MCF-7 breast cancer cells, as well as its invasiveness in an in vitro system. Materials and Methods: The effect of Carboplatin on the viability of MCF-7 breast cancer cells was evaluated using MTT assay at concentrations varying between 1 M to 1 mM. Cells were treated with carboplatin at its IC50 for studies done. Plasma membrane of control and treated cells was isolated and their protein content were quantified. Lipids from total cell homogenate and from the isolated plasma membrane were extracted and their inorganic phosphate was determined. High Performance Liquid Chromatography was used to separate the extracted lipids from plasma membranes. The effect of carboplatin on MCF-7 cells’ invasiveness was investigated by time lapse assay. Results: Carboplatin at 100 M induced 50% cell death in MCF-7 cells after 24 hours. Higher protein concentrations were observed in treated cells compared to control cells. However, there was no change in the amount of inorganic phosphate of the plasma membrane between treated and control cells. After membrane lipids separation, comparison of treated and control cells showed no change in the pattern of separation between the control and carboplatin treated cells. Small changes were seen in specific lipids that eluted at three different retention times. As for the effect of carboplatin on invasion, the motility of carboplatin treated MCF-7 cells decreased 13.3 % compared to control. Conclusion: We hereby report that carboplatin exhibits an effect on the protein content of the plasma membrane of MCF-7 cells as well as the motility of these cells and their invasiveness.
Author(s)
Rim Dannaoui
Coauthor(s)
Dr. Jamilah Borjac, Dr. Mohammad EL-Dakdouki