title: 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.
abstract: 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 α-(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/NFκB 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.
authors: Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Tiffany Chien-Ting
authors: TC
authors: Lo
authors: Feng-Ming
authors: FM
authors: Hsu
authors: C Allen
authors: CA
authors: Chang
authors: Jason Chia-Hsein
authors: JC
authors: Cheng
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000532:radiotherapy; D000077192:Adenocarcinoma of Lung; D002454:Cell Differentiation / Q000187:drug effects* / Q000528:radiation effects; D002460:Cell Line; D005936:Glucans / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000532:radiotherapy; D008970:Molecular Weight; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D011836:Radiation Tolerance / Q000187:drug effects; D020942:Shiitake Mushrooms / Q000737:chemistry*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
chemical_list: D005936:Glucans; D051197:Toll-Like Receptor 4