Effect of Huaier on Melanoma Invasion, Metastasis, and Angiogenesis

Abstract

Malignant melanoma (MM) is a highly metastatic and malignant cancer. Developing potential drugs with good efficacy and low toxicity for MM treatment is needed. Huaier, extracted from the mushroom Trametes robiniophila Murr, has been widely used in clinical anticancer treatments in China. A previous work done by our group confirmed that Huaier could inhibit cell proliferation and induce apoptosis in human melanoma cells. The current study is aimed at investigating the effects of Huaier on melanoma metastasis and angiogenesis in vitro and in vivo and to explore its possible mechanism of action. Our results showed that Huaier not only significantly inhibited the metastasis of A375 cells at the concentration ranging from 4 to 16 mg/ml (P<0.05), which were determined by the wound healing assay and transwell assay in vitro, but also suppressed the MM tumor growth and metastatic cells to the liver in A375-bearing mice after oral administration at the dose of 5 mg/kg (P<0.05). In addition, Huaier treatment downregulated the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), astrocyte-elevated gene-1 (AEG-1), and N-cadherin, while it upregulated E-cadherin expression in both the A375 cells and tumor tissues, which was detected using western blotting and RT-PCR (P<0.05). Taken together, our data suggests that the antitumor and antimetastatic activities of Huaier are caused by the downregulation of the HIF-1α/VEGF and AEG-1 signaling pathways and by the inhibition of epithelial-mesenchymal transition (EMT). This study provides a new insight into the mechanism of Huaier on antimetastatic therapy and a new scientific basis for comprehensive treatment strategies for MM.

Huaier Inhibits Proliferation, Migration, and Invasion of Cutaneous Squamous Cell Carcinoma Cells by Inhibiting the Methylation Levels of CDKN2A and TP53

“…27 Huaier also exhibits antitumor and antimetastatic activities in malignant melanoma, and it inhibits the epithelial-mesenchymal transition by suppressing HIF-1/VEGF and AEG-1 signaling pathways. 28 In the present work, we revealed the function of Huaier in CSCC, showing that Huaier repressed the proliferation, migration, and invasion of CSCC cells. In addition, inhibition of CDKN2A or TP53 reversed the influence of Huaier treatment on proliferation, migration, and invasion of CSCC cells.…”

Immunoregulatory effects of Huaier (Trametes robiniophila Murr) and relevant clinical applications

“…Animal experiments provide strong evidence to the safety of Huaier. Various aspects of Huaier-treated animals that could indicate possible toxicity, such as body weight ( 22 , 31 , 34 , 90 , 119 – 122 ), behavior ( 21 , 30 , 123 ), appetite and food intake ( 112 , 124 ), histology of major organs (heart, liver, kidney, lungs, spleen, pancreas and brain) ( 17 , 20 , 32 , 33 , 125 ), blood assay ( 20 , 23 ), liver and kidney function ( 29 ), and animal survival ( 112 ), have been thoroughly examined in numerous studies. However, almost all of these studies reported negligible signs of toxicity in animals, indicating the safety of Huaier in preclinical studies.…”

Phytochemical Profile and Anticancer Activity from Medicinal Plants Against Melanoma Skin Cancer: A Review

“…Huaier extract significantly inhibits A375 cell metastasis at concentrations ranging from 4-16 mg/ml, in vitro and in vivo. In addition, Huaier extract possesses an antimetastasis effect through HIF-1α/VEGF and AEG-1 signaling pathways and inhibition of the epithelial-mesenchymal transition (EMT) by downregulating hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), astrocyte-elevated gene-1 (AEG-1), and N-cadherin expression, whereas upregulating E.-cadherin expression in A375 cells and tumor tissue (Su et al, 2020). The anticancer effect of Huaier extract has been confirmed in liver, lung, breast, ovarian, gastric, and prostate cancer .…”