[Mechanism of colon cancer cell apoptosis induced by telocinobufagin: role of oxidative stress and apoptosis pathway]

Nan Fang Yi Ke Da Xue Xue Bao. 2016 Jun 20;36(7):921-6.
[Article in Chinese]

Abstract

Objective: To investigate the effects of telocinobufagin on viability and apoptosis of colorectal cancer (CRC) cells and explore the mechanism of telocinobufagin-induced apoptosis.

Methods: MTT assay was performed to detect the viability of CRC cells exposed to telocinobufagin. Nuclear staining with Hoechst 33342 and flow cytometry were used to analyze the cell death of CRC cells. Expressions of proteins related with cell apoptosis and oxidative stress were determined with Western blotting.

Results: Telocinobufagin decreased the viability of CRC cells in a time- and dose-dependent manner. The presence of karyopycnosis and apoptotic bodies together with the results of flow cytometry suggested that telocinobufagin induced cell apoptosis to cause cell death. Western blotting showed that telocinobufagin exposure of the cells resulted in upregulated p53 and Bax protein expressions and promoted cleavage of caspase 9 and PARP. Telocinobufagin induced phosphorylation of Bad and PARP cleavage, and suppressed phosphorylation of IKBα and TAK1 and expression of survivin in the cells.

Conclusion: Telocinobufagin can decrease the viability of CRC cells by inducing cell apoptosis, which involves p53-mediated Bax activation and inhibition of the IAP pathway.

MeSH terms

  • Apoptosis*
  • Bufanolides / pharmacology*
  • Caspase 9 / metabolism
  • Cell Survival
  • Colorectal Neoplasms / pathology*
  • Humans
  • MAP Kinase Kinase Kinases / metabolism
  • NF-KappaB Inhibitor alpha / metabolism
  • Oxidative Stress*
  • Poly (ADP-Ribose) Polymerase-1 / metabolism
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / metabolism
  • bcl-Associated Death Protein / metabolism

Substances

  • BAD protein, human
  • BAX protein, human
  • Bufanolides
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • bcl-Associated Death Protein
  • NF-KappaB Inhibitor alpha
  • telocinobufagin
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7
  • CASP9 protein, human
  • Caspase 9