A polysaccharide from Trametes robiniophila inhibits human osteosarcoma xenograft tumor growth in vivo

Carbohydr Polym. 2015 Jun 25:124:157-63. doi: 10.1016/j.carbpol.2015.02.016. Epub 2015 Feb 20.

Abstract

In the present study, we isolated and purified one polysaccharide (TRP) from Trametes robiniophila, which had a backbone of 1,3,6- and 1,4-linked glucpyranosyl moieties, with 1-linked arabinofuranosyl and galactopyranosyl terminal at the O-3 position of 1,3,6-linked glucpyranosyl residues. TRP was further evaluated for its antitumor activity against xenografted U-2 OS osteosarcoma in BALB/c nude mice together with the possible mechanism of action. We found that oral administration of TRP significantly suppressed U-2 OS tumor growth in mice via the induction of apoptosis, as evidenced by the increased number of TUNEL-positive cells in tumor tissues. Moreover, TRP administration increased the levels of the proapoptotic Bax protein and decreased the level of the antiapoptotic Bcl-2 protein, thus resulting in a rise of Bax/Bcl-2 ratio. Furthermore, the protein expression of caspase-9, caspase-3 and cleaved PARP became evident in tumor tissues from mice following TRP treatment, but caspase-8 keep unchanged. Besides, overexpression of metadherin (MTDH) was attenuated in tumor tissues of TRP-fed mice. Taken together, these findings suggest that the TRP-induced apoptosis of tumor tissues is through a mitochondria-mediated intrinsic apoptotic pathway.

Keywords: Apoptosis; Polysaccharide; Trametes robiniophila; U-2 OS human osteosarcoma cells; Xenograft tumor.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / drug effects
  • Apoptosis Regulatory Proteins / genetics
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / genetics
  • Cell Adhesion Molecules / drug effects
  • Cell Adhesion Molecules / genetics
  • Fungal Polysaccharides / chemistry
  • Fungal Polysaccharides / therapeutic use*
  • Gene Expression
  • Heterografts / drug effects
  • Humans
  • Membrane Proteins
  • Mice
  • Mice, Nude
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics
  • RNA-Binding Proteins
  • Trametes / chemistry*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Cell Adhesion Molecules
  • Fungal Polysaccharides
  • MTDH protein, human
  • Membrane Proteins
  • RNA-Binding Proteins