Polysaccharide lentinan extracted from the stipe of Lentinus edodes mushroom exerts anticancer activities through the transcriptional regulation of cell cycle progression and metastatic markers in human colon cancer cells

Abstract

The edible mushroom Lentinus edodes has been shown to offer medicinal effects including antifungal, antibacterial, antiviral, antioxidant, as well as anticancer activities. Assessment of bioactivities of extracts of the mushroom indicated that the polysaccharide lentinan possesses the potential bioactivities. Currently, the stipe portion of the mushroom is mostly discarded during industrial food processing, generating a large amount of residues. The hypothesis is that the stipe as the industrial byproduct from the mushroom processing contains the similar bioactive polysaccharide that could be utilized to produce mushroom extracts for treatment of cancer. Therefore the current study was designed to examine the polysaccharide extract from the mushroom stipe and its anticancer bioactivities in human colon cancer cells. The preparation and storage methods used in the production of lentinan polysaccharide were also optimized in the study. An aqueous phase extraction method was used for the lentinan production from the stipe as well as the pileus of Lentinus edodes mushroom (LeS vs LeP). Results showed that the lentinan yield from the stipe is comparable to the pileus. WST‐1 assay indicated that at as little as 125 ug/ml, lentinan extracts from both LeS and LeP exerted inhibitory effects against cell proliferation of human colon cancer cells. Cell cycle analysis using flow cytometry indicated that the anti‐proliferative effect is partly due to the induction of cell cycle arrest at the G0/1 phase. Further analysis of gene expression showed that the cell cycle arrest induced by lentinan treatment was associated with a decrease in the mRNA level of cyclin D1 gene. This is accompanied by the reduction of transcription of oncogenes such as c‐myc and induction of gene expression for stress‐responsive pathways. Moreover, NDRG1 gene, a key regulator of cancer metastasis that was often silenced in metastatic colon cancer cells, was increased by lentinan treatment. Together, the current study demonstrates that Letinous edodes stipe is a valuable source of lentinan. Lentinan from Letinous edodes stipe extract is stable when stored under the freeze‐dried condition or at refrigeration. The anti‐proliferative effects of lentinan in colon cancer cells are the results of cell cycle arrest that was induced by the inhibition of cyclin production, combined with the induction of cellular stress‐responsive pathways as well as the transcription of metastasis suppressor genes.Support or Funding InformationThe research is supported by the Office of International Programs of College of ACES at University of Illinois at Urbana‐Champaign and USDA HATCH fund.