A polysaccharide from pumpkin induces apoptosis of HepG2 cells by activation of mitochondrial pathway

Tumour Biol. 2016 Apr;37(4):5239-45. doi: 10.1007/s13277-015-4338-6. Epub 2015 Nov 10.

Abstract

Purified white polysaccharide (PPW) is a homogenous polysaccharide isolated from pumpkin, with an average molecular weight of 34 kDa. In this study, we aimed at examining the anti-proliferative activity of PPW against hepatocellular carcinoma (HCC) HepG2 cells and the underlying mechanisms. We found that PPW-induced inhibition of cell proliferation in HepG2 cells was associated with the induction of apoptosis. Exposure of HepG2 cells to PPW (100, 200, and 400 μg/mL) resulted in a loss of mitochondrial membrane potential (Δψm) and the release of cytochrome c from the mitochondria to the cytosol. Also, Western blot analysis revealed dose-dependent increase of pro-apoptotic Bax protein and decrease of anti-apoptotic Bcl-2 protein in PPW-treated cells. Besides, caspase-9 and caspase-3 activities were also enhanced in HepG2 cells followed by PPW treatment. Additionally, the cleavage of poly (ADP-ribose) polymerase (PARP) was observed in PPW-treated HepG2 cells, which altogether account for apoptotic cell death. These results suggested that PPW-induced apoptosis involved a caspase-3-mediated mitochondrial pathway and may have potential as a cancer chemopreventive and therapeutic agent for the prevention and treatment of HCC.

Keywords: Apoptosis; Hepatoma; Mitochondria; Polysaccharide; Pumpkin; Purification.

MeSH terms

  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Caspase 3 / genetics
  • Cucurbita / chemistry
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / genetics
  • Polysaccharides / administration & dosage*
  • Polysaccharides / chemistry
  • Signal Transduction / drug effects

Substances

  • Polysaccharides
  • Caspase 3