F2-sulfated polysaccharides of Laetiporus sulphureus suppress triple-negative breast cancer cell proliferation and metastasis through the EGFR-mediated signaling pathway

Sulfated polysaccharides (SPS) are a unique secondary metabolite isolated from Laetiporus sulphureus. This study examined the detailed molecular mechanisms of action of F2, a medium molecular weight SPS of L. sulphureus, on breast cancer MDA-MB-231 cell proliferation and metastasis. Results showed that the sulfate and protein content of F2 were 2.1 % and 15.6 %, respectively. F2 had a molecular weight of 23.8 kDa and did not contain a triple helix conformation. The monosaccharide composition of F2 was mannose, galactose, glucose, and fucose. F2 inhibited MDA-MB-231 cell proliferation mainly by blocking the cell cycle at the G0/G1 phase, which was attributed to the down-regulation of CDK4 and cyclin D1 and the up-regulation of p21 protein expression. F2 suppressed epidermal growth factor receptor (EGFR)-mediated intracellular signaling events, such as phosphorylation of ERK1/2, Akt, and GSK-3β and activation of NF-κB and β-catenin, resulting in the cell cycle arrest. Moreover, F2 significantly reduced the EGFR phosphorylation and expression, and the level of mutant p53 protein. F2 also effectively inhibited breast cancer cell migration and invasion through down-regulating MMP-9 and MMP-2 protein expression. In conclusion, this study demonstrated that F2 exhibited anti-proliferative and anti-metastatic activities against MDA-MB-231 cells by inhibiting the activation of EGFR-mediated signaling pathways.