Abstract 1604: HFE is a new target molecule for cancer treatment

Abstract Iron can enhance cell growth and metabolism. However insufficiently regulated iron can lead iron accumulation, enhancing oxidative stress and subsequent damage to DNA, and finally promote cancer. The HFE protein plays a key role in the regulation of body iron and is part of the innate immune system. HFE is the most commonly occurring polymorphism in Caucasians. The two most common HFE polymorphic alleles are C282Y and H63D. The variant forms of HFE have increased iron accumulation. To see the impact of HFE on the brain tumor development, at first, we determined the HFE expression. HFE strongly express in the brain tumors such as meningioma, glioblastoma, and astrocytoma at immunohistochemistry. Then, to assess the association between HFE variants and growth, we measured cell growth and tumor development. We found that human neuroblastoma cell lines that were stably transfected with the C282Y allelic HFE variant proliferated at a much higher rate than the same cell lines expressing the wild type or H63D gene variant at the cell proliferation assay and counting cell number. Furthermore, nude mice injected with glioma cells with the C282Y allele developed much faster and bigger tumor than the other type of HFE cell lines. Next, we transfected HFE siRNA into the cells to determine if the increased rate of proliferation was directly related to the protein associated with the C282Y allelic variant. HFE siRNA treatment significantly inhibited cell proliferation of C282Y transfected neuroblastoma cells. The effect was dose dependent. The cell growth was over 60 % decreased for cells cultured for 4 days after exposure to 15 nM of HFE siRNA. Meanwhile, cells transfected with non-specific siRNA (negative control) or the transfection reagent (mock) control siRNA showed no evidence of inhibited cell proliferation. HFE siRNA also inhibited cell proliferation of wild type and H63D allele cells. We also observed that HFE siRNA inhibited tumor development in the glioma cells injected nude mice. We are currently studying specific delivery system of HFE siRNA to the tumor cells. In summary, we found that HFE inhibition is enough to prevent cancer cell proliferation and tumor development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1604.