Anti-cancer effect and apoptosis induction of cordycepin through DR3 pathway in the human colonic cancer cell HT-29

Food Chem Toxicol. 2013 Oct:60:439-47. doi: 10.1016/j.fct.2013.07.068. Epub 2013 Aug 11.

Abstract

Cordycepin is known to have many pharmacological effects such as anti-tumorigenic, anti-inflammatory and anti-angiogenic activity. However, cordycepin induced apoptosis through the DR3 pathway in human colon cancer cells has not been studied. The effect of cordycepin on anti-proliferation was investigated in this study. Cordycepin significantly inhibited cell viability in a dose and time-dependent manner. Cordycepin increased sub G1 and G2/M phase arrest on HT-29 cells at the concentration of 100 μM, whereas cordycepin at 200 μM and 400 μM increased G1 phase arrest. Cordycepin induced apoptosis in HT-29 cells in a dose-dependent manner as detected by Hoechst and Annexin V-FITC staining. Intracellular ROS levels were higher in cordycepin treated cells as compared to control cells. The protein related to apoptosis was determined by antibody array. p53 and Bax expression increased treatment with cordycepin for 18 h. DR3, caspase-8, caspase-1, cleaved caspase-3 and cleaved PARP expression increased. These finding suggest that the cordycepin induces apoptosis through the DR3 pathway in human colon cancer HT-29. These findings suggest that cordycepin should be evaluated further as a therapeutic agent in human colon cancer.

Keywords: Apoptosis; Cordycepin; DR3; HT-29 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 8 / genetics
  • Caspase 8 / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Deoxyadenosines / pharmacology*
  • G1 Phase / drug effects
  • HT29 Cells
  • Humans
  • Reactive Oxygen Species
  • Receptors, Tumor Necrosis Factor, Member 25 / genetics
  • Receptors, Tumor Necrosis Factor, Member 25 / metabolism*
  • Signal Transduction*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • Deoxyadenosines
  • Reactive Oxygen Species
  • Receptors, Tumor Necrosis Factor, Member 25
  • TNFRSF25 protein, human
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • CASP3 protein, human
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8
  • cordycepin