A major disadvantage of commonly used chemotherapy is the lack of specificity. Therefore urgent need for action in the form of targeted research is new and specific markers on tumor cells can be directed against the novel therapies given .
A promising approach is the development of antitumor agents in the form of membrane-active cationic Peptiden1 , 2 Without receptors to bind to target these peptides to cells expose negatively charged lipids on the outside of their plasma membrane and lyse their "victim" within minutes. Our biophysical studies on derivatives of natural Abwehrpeptide3 , 4 have shown that these biologically active molecules between different cell membranes may differ. Thus, antimicrobial peptides could be tailored , the sind5 selectively directed against bacterial membranes , cancer cell- active ingredients are in the process of Development6 . The basis for this is the nature of the surface of mammalian membranes. The outside of eukaryotic plasma membranes typically consist of neutral phospholipids , such as phosphatidylcholine (PC) and sphingomyelin (SM ) together , whereas the negatively charged phospholipid phosphatidylserine ( PS) IST7 found only in the inner part of the plasma membrane . Under certain pathological conditions usually this asymmetry may be lost , causing it to an exposure of this negative charged phospholipid PS on the surface of eg Cancer cells occur kann8 . This makes it a point of positively charged peptides.
One challenge is the exposure of PS on tumor cells detected in a simple experiment , and in vitro ( on living cells in culture) and quantified relative to normal cells. For this study , which is carried out under a FWF project at the Institute of Biophysics and Nanosystems Research , cell lines of prostate cancer, kidney cancer , malignant melanoma, a rhabdomyosarcoma and brain tumor on their PS content in the outer lipid layer of their plasma membrane were examined and with the surface compared to that of normal cells , such as melanocytes and synovial cells .
For visualization of PS exposure, the specific binding of fluorescent-labeled Annexin V in the presence of an elevated concentration of Ca2 + was used in the medium, a standard assay which is used for the routine investigation of cells , through which the pre-programmed cell death ( apoptosis). Using fluorescence microscopy, thus could be shown that different tumor cell lines ( Figure 2) , as well as primary cell cultures reflect the specific PS markers on its exterior , while healthy melanocytes expose no PS .
Quantifying the amount of the exposed PS was conducted by fluorescence spectroscopy by means of labeled AnnexinV FITC cells, wherein an up to 15 -fold increase in PS exposure has been found by the cancer cells.
literature
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