The Effects of Dandelion Polysaccharides on Iron Metabolism by Regulating Hepcidin via JAK/STAT Signaling Pathway

Abstract

Recent studies have claimed that iron overload was correlated with the risk of hepatocellular carcinoma (HCC), and our previous studies have also demonstrated that dandelion polysaccharide (DP) suppressed HCC cell line proliferation via causing cell cycle arrest and inhibiting the PI3K/AKT/mTOR pathway, but the effect of DP on metabolism is still not very clear. Here, we aim to clarify the effects of DP on iron metabolism and the underlying mechanism. In this study, we found that DP could reduce iron burden in hepatoma cells and grafted tumors. Hepcidin is a central regulator in iron metabolism. We confirmed that the expression of hepcidin in HCC tumor tissues was significantly higher than that in the adjacent nontumor tissues. The expression of hepcidin was downregulated in the liver of mouse model treatment with DP, as well as in hepatoma cells. Moreover, RNA sequencing and western blot data revealed that DP inhibited the IL-6-activated JAK-STAT signaling pathway. In summary, our results revealed that DP might be a new potential drug candidate for the regulation of iron burden and the treatment of HCC.

Ferroptosis Related Immunomodulatory Effect of a Novel Extracellular Polysaccharides from Marine Fungus Aureobasidium melanogenum

“…Fluorescence intensity was measured by using a fluorescence microplate reader (FilterMax F5, Molecular Devices, Silicon Valley, CA, USA). The immunofluorescence detection of adding Fe 2+ in RAW264.7 cells corresponded with the previous methods [ 39 ].…”

“…After blocking the cells with 5% goat serum at room temperature for 30 min, the cells were later cultured with anti-hepcidin (Abcam, Cambridge, UK) at 4 °C for 24 h. The cells were incubated with a secondary antibody (Proteintech, Chicago, IL, USA) for 1 h. After washing 3 times with PBS, DAPI was applied to stain the nucleus. Immunofluorescent signals were detected under a fluorescence microscope (Thermo Fisher Scientific, Waltham, MA, USA) [ 39 ].…”

Revealing the metabolic mechanism of dandelion extract against A549 cells using UPLC‐QTOF MS

“…In previous studies, the antitumor mechanisms of dandelion extract mainly include anti‐angiogenesis (Ren et al, 2020), downregulation of hepcidin and diminished tumor iron burden (Ren et al, 2021), and targeting of tumor growth‐related RNA (Zhu et al, 2017). Our study proposed for the first time that dandelion extract inhibited tumor cell growth by disturbing glycerophospholipid metabolism and purine metabolism, which may provide a novel insight into the anticancer effects of dandelion extract.…”

Interaction between macrophages and ferroptosis

“…IL-6 affect iron levels in cells by controlling the transcription of hepcidin which is a short cysteine-rich peptide hormone that can influence intestinal absorption and the release of iron in macrophages Fe stores. The transcription of hepcidin is mediated by IL-6 via the activation of JAK-STAT3 pathway [ 43 , 44 ], and the expression of hepcidin is found to be activated by BMP/SMAD pathway [ 45 ]. Hepcidin first binds to ferroportin (FPN) and cause internalization of hepcidin-FPN that is soon degraded into lysosomes [ 46 ].…”