Agaricus bisporus β-(1 → 6)-d-glucan induces M1 phenotype on macrophages and increases sensitivity to doxorubicin of triple negative breast cancer cells

Carbohydr Polym. 2022 Feb 15:278:118917. doi: 10.1016/j.carbpol.2021.118917. Epub 2021 Nov 20.

Abstract

Mushroom β-d-glucans have demonstrated immunomodulatory activity, which is initiated by their recognition by specific receptors on immune system cells surfaces. Studies indicated that β-d-glucans may present a synergistic effect with chemotherapy drugs. In this study, a linear β-(1 → 6)-d-glucan (B16), isolated from A. bisporus and previously characterized (Mw: 8.26 × 104 g/mol), was evaluated about its capacity to modulate THP-1 macrophages towards an M1 phenotype and induce an antitumoral activity. This was evidenced by the production of pro-inflammatory markers upon B16 treatment (30; 100 μg/mL). The breast tumor cells (MDA-MB-231) viability was not affected by treatment with B16, however, their viability markedly decreased upon treatment with the drug doxorubicin. The results showed a synergic effect of B16 and doxorubicin, which reduced the viability of MDA-MB-231 cells by 31%. Furthermore, B16 treatment provided a sustainable M1 state environment and contributed to increase the sensitivity of breast cancer cells to the doxorubicin treatment.

Keywords: Agaricus bisporus, β-(1 → 6)-d-glucan; Antioxidant activity; Antitumoral effect; Immunomodulatory activity; Triple-negative breast cancer cells.

MeSH terms

  • Agaricus / chemistry*
  • Animals
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Screening Assays, Antitumor
  • Humans
  • Immunologic Factors / chemistry
  • Immunologic Factors / pharmacology*
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • Phenotype
  • Polysaccharides / chemistry
  • Polysaccharides / pharmacology*
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / immunology
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Antibiotics, Antineoplastic
  • Immunologic Factors
  • Polysaccharides
  • Doxorubicin

Supplementary concepts

  • Agaricus bisporus