PUMA and survivin are involved in the apoptosis of HepG2 cells induced by microcystin-LR via mitochondria-mediated pathway

Chemosphere. 2016 Aug:157:241-9. doi: 10.1016/j.chemosphere.2016.05.051. Epub 2016 May 26.

Abstract

The present study aimed to determine the cytotoxicity of microcystin-LR (MC-LR) on the human hepatocellular carcinoma (HepG2) cells in order to elucidate the mechanism of apoptosis induced by MC-LR. Morphological evaluation results showed that MC-LR induced time- and concentration-dependent apoptosis in HepG2 cells. The biochemical assays revealed that MC-LR-exposure caused overproduction of reactive oxygen species (ROS), cyclooxygenase-2 activity alteration, cytochrome c release, and remarkable activation of caspase-3 and caspase-9 in HepG2 cells, indicating that MC-LR-induced apoptosis is mediated by mitochondrial pathway. Moreover, we also found that p53 and Bax might play an important role in MC-LR-induced apoptosis in HepG2 cells in which PUMA and survivin were involved. However, further studies are necessary to elucidate the possible functions of PUMA and survivin in MC-LR-induced apoptosis in HepG2 cells.

Keywords: Apoptosis; HepG2; Microcystin-LR; Mitochondria-mediated pathway; PUMA; Survivin.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Cytotoxins / toxicity*
  • Hep G2 Cells
  • Hepatitis / etiology
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / metabolism
  • Liver Neoplasms / chemically induced
  • Marine Toxins
  • Microcystins / toxicity*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Risk Assessment
  • Survivin

Substances

  • Apoptosis Regulatory Proteins
  • BBC3 protein, human
  • BIRC5 protein, human
  • Cytotoxins
  • Inhibitor of Apoptosis Proteins
  • Marine Toxins
  • Microcystins
  • Proto-Oncogene Proteins
  • Survivin
  • cyanoginosin LR