Traditional Chinese Medicine Extract from Huaier Increases the Expression of Duffy Antigen Receptor for Chemokines and Reduces the Expression of Its Ligands
Abstract:Aims The aim of the present study is to investigate whether the aqueous extract from Huaier, a traditional Chinese medicine (TCM), can affect the expression of Duffy antigen receptor for chemokines (DARC) and its ligands. Moreover, we compare the status of DARC in primary and metastatic breast cancer tissues from the same patient. Methods Immunohistochemistry was used to detect the expression of DARC in primary and metastatic focuses in 30 patients with breast cancer. The effect of Huaier aqueous extract on th… Show more
“…Previous studies have confirmed that Huaier can play an antitumor role by regulating immune functions, such as increasing the index of immune organs, regulating the number of lymphocytes and regulating the secretion of cytokines. Ying Chen et al [ 28 ] found that Huaier could increase the expression of Duffy antigen receptor for chemokines (DARC) and reduce its ligands, such as CC chemokine ligand 2 (CCL-2), CXC chemokine ligand 8 (CXCL-8, IL-8), matrix metalloproteinase 2 (MMP-2), and CXC chemokine ligand 1 (CXCL-1). DARC plays a negative role in breast cancer metastasis.…”
Background
Pyroptosis is a highly programmed inflammatory cell death process that represents an innate immune response. In this study, the occurrence of pyroptosis in rat mesangial cells (RMCs) and the effect of Huaier (Trametes robiniophia Murr) on this process were investigated.
Methods
RMCs were incubated with OX7 antibodies (0.5 μg/ml, 2.5 μg/ml, 10 μg/ml), normal rat serum (NRS) and Huaier (1 mg/ml, 5 mg/ml, 10 mg/ml). RMC morphology was observed under a light microscope and by immunofluorescence. Lactate dehydrogenase (LDH) release was assessed using the CytoTox 96 Non-Radioactive Cytotoxicity Assay Kit. Western blot assays were performed, and then the RMCs were incubated with the methylase DNMT3B and the demethylase 5-aza-2′-deoxycytidine.
Results
Morphological, LDH, immunofluorescence and western blot analyses showed that RMCs were lysed when stimulated with OX7 antibodies and NRS. RMC lysis released inflammatory cytokines (interleukin-18, interleukin-1β, monocyte chemoattractant protein-1 and intracellular adhesion molecule-1), and Huaier protected RMCs by controlling lysis and the levels of inflammatory cytokines. Lysis was mediated by pyroptosis due to the positive expression of GSDME. The methylase DNMT3B reduced the expression of GSDME induced by OX7 together with NRS. Furthermore, Huaier significantly suppressed the expression of GSDME, which was increased by 5-aza-2’-deoxycytidine.
Conclusions
Pyroptosis might occur in RMCs, and Huaier can protect RMCs by upregulating the methylation of a group of molecules.
“…Previous studies have confirmed that Huaier can play an antitumor role by regulating immune functions, such as increasing the index of immune organs, regulating the number of lymphocytes and regulating the secretion of cytokines. Ying Chen et al [ 28 ] found that Huaier could increase the expression of Duffy antigen receptor for chemokines (DARC) and reduce its ligands, such as CC chemokine ligand 2 (CCL-2), CXC chemokine ligand 8 (CXCL-8, IL-8), matrix metalloproteinase 2 (MMP-2), and CXC chemokine ligand 1 (CXCL-1). DARC plays a negative role in breast cancer metastasis.…”
Background
Pyroptosis is a highly programmed inflammatory cell death process that represents an innate immune response. In this study, the occurrence of pyroptosis in rat mesangial cells (RMCs) and the effect of Huaier (Trametes robiniophia Murr) on this process were investigated.
Methods
RMCs were incubated with OX7 antibodies (0.5 μg/ml, 2.5 μg/ml, 10 μg/ml), normal rat serum (NRS) and Huaier (1 mg/ml, 5 mg/ml, 10 mg/ml). RMC morphology was observed under a light microscope and by immunofluorescence. Lactate dehydrogenase (LDH) release was assessed using the CytoTox 96 Non-Radioactive Cytotoxicity Assay Kit. Western blot assays were performed, and then the RMCs were incubated with the methylase DNMT3B and the demethylase 5-aza-2′-deoxycytidine.
Results
Morphological, LDH, immunofluorescence and western blot analyses showed that RMCs were lysed when stimulated with OX7 antibodies and NRS. RMC lysis released inflammatory cytokines (interleukin-18, interleukin-1β, monocyte chemoattractant protein-1 and intracellular adhesion molecule-1), and Huaier protected RMCs by controlling lysis and the levels of inflammatory cytokines. Lysis was mediated by pyroptosis due to the positive expression of GSDME. The methylase DNMT3B reduced the expression of GSDME induced by OX7 together with NRS. Furthermore, Huaier significantly suppressed the expression of GSDME, which was increased by 5-aza-2’-deoxycytidine.
Conclusions
Pyroptosis might occur in RMCs, and Huaier can protect RMCs by upregulating the methylation of a group of molecules.
“…With the finding of role in cancer prevention and treatment, TCM has been one of important alternatives among the new developing anti-tumor drugs possessing low toxicity, side effects, low cost [10]. Huaier extract has been evidenced with anti-tumor effect in numerous in pre-clinical studies.…”
Section: Discussionmentioning
confidence: 99%
“…In recent years, many traditional Chinese herbal medicines (TCM) have exerted promising anti-cancer efficacy and applied in clinical settings as complementary anti-tumor agents [10]. Huaier, also known as Trametes robiniophila Murr, has been applied as a TCM for more than 1,600 years.…”
Huaier extract, the main active constituent proteoglycan, has anti-tumor activity in various experimental and clinical settings. However, the potential anti-neuroblastoma and associated mechanisms have not been investigated. Therefore, in this study, we aimed to elucidate the potential role of Huaier extract in 3 human neuroblastoma cell lines. Our study demonstrated that incubation with Huaier extract resulted in a marked decrease in cell viability in a dose-dependent manner. Huaier extract induced cell cycle arrest at G0/G1 phase in neuroblastoma and decreased the cell cycle related protein expression of cyclin D3. Western blotting analysis also showed that Huaier extract induced neuroblastoma cell apoptosis and autophagy. Signaling analysis indicated that Huaier extract suppressed the MEK/ERK and mTOR signaling pathways simultaneously. In conclusion, we verify that Huaier extract causes cell proliferation inhibition, apoptosis, autophagy, and cell cycle arrest in G0/G1 phase via MEK/ERK and mTOR signaling. Huaier extract may act as a complementary agent for treating neuroblastoma.
“…Because the expression of DARC is upregulated but that of its ligand is down-regulated among breast cancer cells in Huaier incubation, Huaier may negatively regulate breast cancer by upregulating DARC ( Figure 2 ). 35 Figure 2 Huaier inhibits cell proliferation and metastasis by upregulating DARC and downregulating its ligands. Huaier suppresses EMT by downregulating twist to inhibit tumor metastasis while the medicine inhibits metastasis by inhibiting c-Myc-Bmi1 signaling pathway.…”
Section: Breast Cancermentioning
confidence: 99%
“…expression of DARC is upregulated but that of its ligand is down-regulated among breast cancer cells in Huaier incubation, Huaier may negatively regulate breast cancer by upregulating DARC (Figure 2). 35 The mTOR/S6K Signaling Pathway…”
Huaier (
Trametes robiniophila Murr
), a Chinese traditional herb of medicine, has demonstrated promising curative effects in clinical treatment for various tumors. There are documented experiments showing the biological functions of Huaier with its antineoplastic molecular mechanisms: restraining proliferation and metastasis, arresting cell cycle, inducing apoptosis, pyrosis, and autophagy, anti-intratumoral angiogenesis, attenuating characteristics of tumor stem-like cells, interfering with the function of the tumor-related immune system, reversing drug resistance, and enhancing the sensitivity to chemotherapeutic drugs, etc. In addition, studies suggest that non-coding RNA (ncRNA) acts a pivotal part in cancer occurrence and development, and demonstrates that Huaier adjusts the performance of certain lncRNA (long non-coding RNA) and proceeds to affect the microRNA and its target genes, rendering an anti-tumor effect. Huaier also modulates the expression of lncRNA to attenuate the activity of ncRNA-sponged microRNA and then inhibits the expression of downstream target genes. We summarize and illustrate the experimentally confirmed anti-cancer molecular mechanisms of Huaier, to inspire new ideas for researchers in relevant fields.
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