Abstract
BackgroundPolysaccharides extracted from the Phellinus linteus (PL) mushroom are known to possess anti-tumor effects. However, the molecular mechanisms responsible for the anti-tumor properties of PL remain to be explored. Experiments were carried out to unravel the anticancer effects of PL.MethodsThe anti-cancer effects of PL were examined in SW480 colon cancer cells by evaluating cell proliferation, invasion and matrix metallo-proteinase (MMP) activity. The anti-angiogenic effects of PL were examined by assessing human umbilical vein endothelial cell (HUVEC) proliferation and capillary tube formation. The in vivo effect of PL was evaluated in an athymic nude mouse SW480 tumor engraft model.ResultsPL (125-1000 μg/mL) significantly inhibited cell proliferation and decreased β-catenin expression in SW480 cells. Expression of cyclin D1, one of the downstream-regulated genes of β-catenin, and T-cell factor/lymphocyte enhancer binding factor (TCF/LEF) transcription activity were also significantly reduced by PL treatment. PL inhibited in vitro invasion and motility as well as the activity of MMP-9. In addition, PL treatment inhibited HUVEC proliferation and capillary tube formation. Tumor growth of SW480 cells implanted into nude mice was significantly decreased as a consequence of PL treatment, and tumor tissues from treated animals showed an increase in the apoptotic index and a decrease in β-catenin expression. Moreover, the proliferation index and microvessel density were significantly decreased.ConclusionsThese data suggest that PL suppresses tumor growth, invasion, and angiogenesis through the inhibition of Wnt/β-catenin signaling in certain colon cancer cells.
Highlights
Polysaccharides extracted from the Phellinus linteus (PL) mushroom are known to possess anti-tumor effects
We previously demonstrated that PL has an antiproliferative effect for SW480 colon cancer cells and the growth inhibition is mediated by induction of apoptosis and G2/M cell cycle arrest which are associated with decrease in Bcl-2, increase of the release of cytochrome c, and reduced expression of cyclin B1 [6]
human umbilical vein endothelial cell (HUVEC) were cultured in gelatin-coated plates with Endothelial Basal Medium-2 (EBM-2) supplemented with 10 mL fetal bovine serum (FBS), 0.2 mL hydrocortisone, 2 mL human fibroblast growth factor-basic, 0.5 mL vascular endothelial growth factor (VEGF), 0.5 mL R3-IGF-1, 0.5 mL ascorbic acid, 0.5 mL human epidermal growth factor, 0.5 mL GA-1000, 0.5 mL heparin (EBM-2 Bullet kit, Clonetics) and incubated at 37°C in a humidified incubator containing 5% CO2
Summary
Polysaccharides extracted from the Phellinus linteus (PL) mushroom are known to possess anti-tumor effects. The molecular mechanisms responsible for the anti-tumor properties of PL remain to be explored. Recent advances in chemotherapeutic agents in CRC have been achieved, Mushroom polysaccharides are widely being used as nonspecific immunostimulants for cancer patients in Asian countries. The Polysaccharide isolated from Phellinus linteus (PL) is an immunomudulatory agent with a molecular weight of 153 kDa [2]. PL stimulates the proliferation of T lymphocytes and activates B cells [3], induces secretory and celluar macrophage response [4], and inhibits tumor growth and metastasis through the immunopotentiation [5]. It had been suggested that antitumor effect are immunomodulatory, but may result from a direct action on tumor cells
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