Colorectal cancer (CRC) is one of leading cause of mortality in western countries and novel
treatment strategies are required. The medicinal application of mushrooms has been used in
traditional medicine in many oriental countries. Polysaccharide-rich extracts obtained from certain
medicinal mushroom species have shown antitumor effects in different experimental models. In the
present study, we have developed polysaccharide-rich extracts from Trametes versicolor (TV) and
Grifola frondosa (GF) fruit bodies. We aim to evaluate the anticancer effects of these
polysaccharide-rich extracts in LoVo and HT-29 human colon cancer cells. The in vitro effects were
determined by cytotoxicity assay, proliferation assay, wound healing assay and invasion assay.
Moreover, the effect on anchorage independent-cell growth was also determined. Our results
showed that TV and GF extracts did inhibit human colon cell proliferation and induce cytotoxicity.
Furthermore, both fungal extracts significantly inhibited oncogenic potential, cell migration and
invasion in colon cancer cells. In addition, extracts induce a more epithelial phenotype, observed by
phase contrast images, together with an increase expression of the E-cadherin epithelial marker,
detected by western-blotting analyses. Moreover, by using gelatin zymography assays, it was
detected a decrease of MMP-2 enzyme activity, a crucial metalloproteinase important for the
degradation of the extracellular matrix. Finally, the combination of the extracts with one the most
clinical used agents for colorectal cancer, 5-fluorouracil, increases cell cytotoxicity. Taken together
our results underscore a potential antitumor effect of polysaccharide-rich extracts obtained from
TV and GF in human colon cancer cells lines. These finding may contribute to the reported health
effects of fungal extracts.