The Effects of Angelica Sinensis Polysaccharide on Tumor Growth and Iron Metabolism by Regulating Hepcidin in Tumor-Bearing Mice

Abstract

Background/Aims: Iron plays a fundamental role in cell biology and its concentration must be precisely regulated. It is well documented that excess iron burden contributes to the occurrence and progression of cancer. Hepcidin secreted by liver plays an essential role in orchestrating iron metabolism. In the present study, we aimed to investigate the ability of angelica sinensis polysaccharide (ASP) to decrease iron burden in tumor-bearing mice and the mechanism of ASP regulation hepcidin expression. Methods: Western blot, RT-PCR, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA) were used to detect the regulation of hepcidin and related cytokines by ASP. The role of ASP in tumor proliferation was investigated using in vivo assays. Iron depositions and iron concentrations in organs were determined by hematoxylin-eosin (H&E) staining and atomic absorption spectrophotometer. Results: We found that ASP could inhibit tumor growth in mice xenografted with 4T1 and H22 cancer cells. In vivo experiments also showed that ASP could potently regulate hepcidin expression in liver and serum and decrease iron burden in liver, spleen and grafted tumors in mouse model. Treatment with ASP in hepatic cell lines reproduced comparable results in decreasing hepcidin as in mouse liver. Furthermore, we found that ASP markedly suppressed the expression of interleukin-6 (IL-6), JAK2, p-STAT3, and p-SMAD1/5/8 in liver, suggesting that JAK/STAT and BMP-SMAD pathways were involved in the regulation of hepcidin expression by ASP. We also found down-regulation of iron-related cytokines in ASP treated mice. Conclusion: The present study provides new evidence that ASP decreases hepcidin expression, which can reduce iron burden and inhibit tumor proliferation. These findings might aid ASP developed as a potential candidate for cancer treatment in patients with iron overload.

Dandelion Polysaccharide Exerts Anti-Angiogenesis Effect on Hepatocellular Carcinoma by Regulating VEGF/HIF-1α Expression

“…Many natural products have been found to possess many bioactivities, such as anti-tumor effects, anti-oxidant function, and anti-inflammatory activity (Newman and Cragg, 2012;Chen et al, 2016a;Chen et al, 2016b;Ren et al, 2018). Dandelion is a popular Chinese medicinal herb widely grown in lawns, roadsides as well as shores of water ways and often consumed as a vegetable.…”

Peer Review #1 of "Identification of key miRNAs in the progression of hepatocellular carcinoma using an integrated bioinformatics approach (v0.1)"

“…Manuscript to be reviewed response (MARCO) , iron homeostasis regulation (HAMP) (F Ren et al, 2018), proteoglycans synthesis (ECM1 (H Chen et al, 2011), DCN(Z Horvath et al, 2014)) have been reported to be associated with the progression or prognosis of HCC. Especially, two miRNAs-hsa-miR-106b and hsa-miR-195, which were verified as HCC classifiers in two independent profiles, have been also implicated in regulating HCC development.…”

The Bioactivities and Potential Clinical Values of Angelica Sinensis Polysaccharides

“…6 Additionally, it also could exert its anti-tumor activity by regulating iron metabolism, which might make hepcidin, IL-6, ferritin, transferrin (Tf), transferrin receptor 1 (TfR1), and TfR2 become targets of tumor therapy. 15,32 ASP could inhibit the proliferation, migration, invasion, and induce apoptosis of SH-SY5Y cells. It might inactivate PI3K/Akt and JAK/STAT signaling pathways via down-regulating miR-675 in SH-SY5Y cells, thereby inhibiting the tumorigenicity of SH-SY5Y cells.…”