Ginseng polysaccharide serves as a potential radiosensitizer through inducing apoptosis and autophagy in the treatment of osteosarcoma

Kaohsiung J Med Sci. 2017 Nov;33(11):535-542. doi: 10.1016/j.kjms.2017.07.001. Epub 2017 Aug 18.

Abstract

Recent studies have confirmed that the combined use of anti-cancer drugs with ionizing radiation (IR) could improve the sensitivity of osteosarcoma (OS) cells. Therefore, it is necessary to identify potential effective drugs for the enhancement of IR-radiosensitivity. In the current study, we found that 20, 10, 5, and 1 μM of ginseng polysaccharide (GPS) significantly suppressed MG-63 cell viability with or without γ-ray radiation in a dose- and time-dependent manner. Strikingly, 20 μM of GPS combined with 5 Gy treatment suppressed colony formation capacity by nearly 13.75∼fold compared with IR treatment alone. Our results showed that GPS could markedly induce early apoptosis and autophagy in MG-63 cells. A higher drug concentration and a greater exposure dose were directly associated with more apoptosis and autophagy in cells. Western blot analysis showed that GPS decreased the phosphorylation of p38 and AKT as well as the protein expression of Bax and cleaved-caspase3. In summary, GPS inhibited proliferation and increased apoptosis and autophagic death in OS cells, indicating that GPS may be a potential effective auxiliary drug for improving the IR sensitivity of OS patients.

Keywords: Ginseng polysaccharide; Ionizing radiation therapy; Osteosarcomas; Radiosensitizer.

MeSH terms

  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Autophagy / drug effects
  • Autophagy / genetics
  • Autophagy / radiation effects
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Gamma Rays
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteoblasts / radiation effects
  • Panax / chemistry*
  • Phosphorylation / drug effects
  • Phosphorylation / radiation effects
  • Plant Extracts / chemistry
  • Polysaccharides / isolation & purification
  • Polysaccharides / pharmacology*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Radiation Tolerance
  • Radiation-Sensitizing Agents / isolation & purification
  • Radiation-Sensitizing Agents / pharmacology*
  • Signal Transduction
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • BAX protein, human
  • Plant Extracts
  • Polysaccharides
  • Radiation-Sensitizing Agents
  • bcl-2-Associated X Protein
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • Caspase 3