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BMC Cancer  2011 

A novel transferrin receptor-targeted hybrid peptide disintegrates cancer cell membrane to induce rapid killing of cancer cells

DOI: 10.1186/1471-2407-11-359

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In vitro: We assessed the cytotoxicity of TfR-lytic hybrid peptide for 12 cancer and 2 normal cell lines. The specificity for TfR is demonstrated by competitive assay using TfR antibody and siRNA. In addition, we performed analysis of confocal fluorescence microscopy and apoptosis assay by Annexin-V binding, caspase activity, and JC-1 staining to assess the change in mitochondria membrane potential. In vivo: TfR-lytic was administered intravenously in an athymic mice model with MDA-MB-231 cells. After three weeks tumor sections were histologically analyzed.The TfR-lytic hybrid peptide showed cytotoxic activity in 12 cancer cell lines, with IC50 values as low as 4.0-9.3 μM. Normal cells were less sensitive to this molecule, with IC50 values > 50 μM. Competition assay using TfR antibody and knockdown of this receptor by siRNA confirmed the specificity of the TfR-lytic hybrid peptide. In addition, it was revealed that this molecule can disintegrate the cell membrane of T47D cancer cells just in 10 min, to effectively kill these cells and induce approximately 80% apoptotic cell death but not in normal cells. The intravenous administration of TfR-lytic peptide in the athymic mice model significantly inhibited tumor progression.TfR-lytic peptide might provide a potent and selective anticancer therapy for patients.The transferrin receptor (TfR) is a cell-membrane-associated glycoprotein involved in the cellular uptake of iron and the regulation of cell growth [1]. Iron is a required cofactor of heme and nonheme proteins involved in a variety of cellular processes including metabolism and DNA synthesis [2,3]. Therefore, various studies have shown elevated levels of TfR expression on cancer cells when compared with their normal counterparts [4-13]. Bladder-transitional cell carcinomas, breast cancer, glioma, lung adenocarcinoma, chronic lymphocytic leukemia, and non-Hodgkin's lymphoma also showed increased TfR expression that correlated with tumor grade and stage or prognosi


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