Malignant melanoma is an invasive and highly aggressive skin cancer that-if diagnosed-poses a serious threat to the patient's health and life. In this work, a novel purified cell-wall polysaccharide (termed Abwp) was obtained from the discarded stipe of Agaricus bisporus (A. bisporus) and characterized to be a novel homogeneous polysaccharide consisted of a β-(1 → 4)- glucosyl backbone with β-(1 → 2) and (1 → 6)-d-glucosyl side-chains. The anti-melanoma effects of Abwp and its associated mechanisms in mice were then explored using in vitro and in vivo approaches. In vitro results showed that Abwp inhibited B16 melanoma cell proliferation and promoted their apoptosis in both time- and dose-dependent manners. In B16 cells induced with tumor necrosis factor (TNF-α), Abwp significantly decreased the protein expression of inflammatory-related signaling pathway (e.g., p38 MAPK and NF-κB) in time-, concentration-, and dose-dependent manners. Moreover, Abwp blocked nuclear entry of NF-κB-p65. In an in vivo mouse model featuring neoplasm transplantation with B16 melanoma cells, Abwp significantly inhibited the growth and proliferation of mouse melanoma. Hematoxylin staining showed that the invasion of melanoma cells into the lung tissue of the Abwp-treated group was significantly reduced. Immunohistochemical analysis showed that the expression of proliferation cell nuclear antigen (PCNA), N-cadherin, MMP-9, and Snail in the lung of mouse was significantly inhibited. Immunofluorescence showed that Abwp significantly interfered with the nuclear transcription of NF-κB-p65 in a dose-dependent manner. Collectively, these results showed that Abwp mediated p38 MAPK and NF-κB signaling pathways to inhibit the inflammatory response and malignant proliferation and metastasis of melanoma in mice.
Keywords: Agaricus bisporus; Melanoma; NF-κB; Polysaccharide; TNF-α; p38 MAPK.
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