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báo cáo khoa học: "Anticancer activity of the iron facilitator LS081"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Anticancer activity of the iron facilitator LS081 | Journal of Experimental Clinical Cancer Research Li et al. Journal of Experimental Clinical Cancer Research 2011 30 34 http www.jeccr.eom content 30 1 34 RESEARCH Open Access Anticancer activity of the iron facilitator LS081 Zhen Li Hiroki Tanaka Floyd Galiano and Jonathan Glass Abstract Background Cancer cells have increased levels of transferrin receptor and lower levels of ferritin an iron deficient phenotype that has led to the use of iron chelators to further deplete cells of iron and limit cancer cell growth. As cancer cells also have increased reactive oxygen species ROS we hypothesized that a contrarian approach of enhancing iron entry would allow for further increased generation of ROS causing oxidative damage and cell death. Methods A small molecule library consisting of 11 000 compounds was screened to identify compounds that stimulated iron-induced quenching of intracellular calcein fluorescence. We verified the iron facilitating properties of the lead compound LS081 through 55Fe uptake and the expression of the iron storage protein ferritin. LS081-induced iron facilitation was correlated with rates of cancer cell growth inhibition ROS production clonogenicity and hypoxia induced factor HIF levels. Results Compound LS081 increased 55Fe uptake in various cancer cell lines and Caco2 cells a model system for studying intestinal iron uptake. LS081 also increased the uptake of Fe from transferrin Tf . LS081 decreased proliferation of the PC-3 prostate cancer cell line in the presence of iron with a lesser effect on normal prostate 267B1 cells. In addition LS081 markedly decreased HIF-1a and -2a levels in DU-145 prostate cancer cell line and the MDA-MB-231 breast cancer cell lines stimulated ROS production and decreased clonogenicity. Conclusions We have developed a high through-put screening technique and identified small molecules that stimulate iron uptake both from ferriTf and non-Tf bound iron. These iron facilitator compounds displayed properties .