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Background: Deferoxamine (DFO) is a commonly used iron chelator, which can reduce the iron levels in cells. DFO is normally used to treat iron-overload disease, including some types of cancer. However, our previous studies revealed that DFO treatment significantly increased the iron concentrations in triple-negative breast cancer cells (TNBCs) resulting in enhanced cell migration. But the mechanism of DFO-induced increasing iron uptake in aggressive TNBCs still remained unclear. Materials and methods: Iron metabolism-related proteins in aggressive breast cancer MDA-MB-231, HS578T and BT549 cells and nonaggressive breast cancer MCF-7 and T47D cells were examined by immunofluorescence and Western blotting. The possible regulatory mechanism was explored by Western blotting, co-incubation with neutralizing antibodies or inhibitors, and transwell assay. Results: In this study, we found that DFO treatment significantly increased the levels of iron uptake proteins, DMT1 and TfR1, in aggressive TNBCs. Moreover, both TfR1 and DMT1 expressed on cell membrane were involved in high iron uptake in TNBCs under DFO-induced iron deficient condition. For the possible regulatory mechanism, we found that DFO treatment could promote a high expression level of IL-6 in aggressive MDA-MB-231 cells. The activated IL-6/PI3K/AKT pathway upregulated the expression of iron-uptake related proteins, TfR1 and DMT1, leading to increased iron uptakes. Conclusion: We demonstrated that DFO could upregulate expression of TfR1 and DMT1 , which enhanced iron uptake via activating IL-6/PI3K/AKT signaling pathway in aggressive TNBCs.

Pulmonary fibrosis (PF) could severely disrupt the normal lung architecture and function with fatal consequences. Currently, there is no effective treatment for PF or idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the effects of Sodium Houttuyfonate (SH) on bleomycin (BLM) induced PF mice model. Our results indicated that SH could attenuate BLM induced lung injury by reducing the inflammation, fibrogenesis and lung/body weight ratio. The proposed mechanisms for the protective effects of SH include: 1) improvement of pulmonary function in BLM mice, for instance, it can elevate the vital capacity (VC), increase the forced expiratory flow at 50% of forced vital capacity (FEF50) and improve other pulmonary function indices; 2) inhibition of collagen formation in BLM mice; 3) attenuation of the elevation of inflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), which are triggered by BLM administration; 4) reduction of the mRNA level and protein production of transforming growth factor-β1 (TGF-β1) in BLM mice. Furthermore, it was found that the protective effects of SH against BLM induced PF in mice was comparable to that of prednisone acetate (PA) tablets, a widely used drug for immunological diseases. Although Houttuynia Cordata Thunb has been widely used in China for lung infection and inflammation, the mechanism has not yet been fully elucidated. Our study provides the evidence that SH is an effective compound against pulmonary injury, irritation and fibrogenesis.