Branched α-(1,4) Glucans from Lentinula edodes (L10) in Combination with Radiation Enhance Cytotoxic Effect on Human Lung Adenocarcinoma through the Toll-like Receptor 4 Mediated Induction of THP-1 Differentiation/Activation

This work investigated the role of structure in the binding of polysaccharides from 10 regionally different strains of Lentinula edodes to Toll-like receptor 4 (TLR-4) on monocytes (THP-1) and the potential effect of this interaction on tumor cell viability. Principal component analysis and multiple linear regression identified arabinose, glucose 1 -> 4 linkage, and molecular weights about 2700 and 534 kDa as the significant determinant factors associated with TLR-4 binding activity. The branched alpha-(1,4)-glucan (L10) had the strongest ability to bind to TLR-4 and induce THP-1 cell differentiation. L10 induction of the THP-1 cell differentiation, superoxide production, and cytokine production followed the TLR-4/MyD88/IKK/NF kappa B pathway. Coculture of irradiated human lung adenocarcinoma A549 cells with L10-activated THP-1 cells resulted in significantly decreased percentage of viable A549 cells from 66 to 37% (p = 0.018), increased levels of superoxide, interleukin-8, and RANTES, and decreased levels of angiogenin and vascular endothelial growth factor. The results indicate that L10-activated monocytes have the potential to boost the antitumor immune response and antitumor activity of radiotherapy.