Characterization and anti-tumor bioactivity of astragalus polysaccharides by immunomodulation

Int J Biol Macromol. 2020 Feb 15:145:985-997. doi: 10.1016/j.ijbiomac.2019.09.189. Epub 2019 Oct 24.

Abstract

Astragalus polysaccharide (APS) has attracted growing interests in the field of anti-cancer by direct killing effect and improving immune function. In this study, the structure and composition of APS was determined, following the evaluation of in vitro and in vivo anti-tumor activity of APS targeted macrophages and host immune system based on immunoregulated strategy. The results indicated that APS had no direct cytotoxicity against 4T1 cells, but APS mediated macrophages could significantly inhibit the growth of 4T1 cells by the induction of cell cycle arrest (G2 phase) and cell apoptosis. APS mediated macrophages promoted the apoptosis of 4T1 cells mainly through the mitochondrial apoptosis pathway. The in vivo findings demonstrated that APS could markedly improve the thymus index and spleen index, and restore the structure of the damaged thymus and spleen tissue. APS could significantly enhance the proliferation of spleen lymphocytes and increase phagocytosis of peritoneal macrophages in mice. Furthermore, APS was capable of up-regulating the expression of IL-2, TNF-α and IFN-γ in peripheral blood. APS combined with 5-FU could improve the anti-tumor effect accompanied by the immunosuppressive alleviation of 5-FU on immune system, which may be suitable as an immune adjuvant for chemotherapy.

Keywords: Astragalus polysaccharide; Cell apoptosis; Immunoregulation; Macrophages activation; Mitochondria pathway.

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Astragalus Plant / chemistry*
  • Breast Neoplasms
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytokines / blood
  • Disease Models, Animal
  • Female
  • Immunomodulation / drug effects*
  • Macrophages / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mitochondria / metabolism
  • Phagocytosis / drug effects
  • Polysaccharides / chemistry*
  • Polysaccharides / pharmacology*
  • RAW 264.7 Cells
  • Spleen / immunology
  • Thymus Gland

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • Cytokines
  • Polysaccharides
  • Caspase 3
  • Caspase 9