Phycocyanin-mediated apoptosis in AK-5 tumor cells involves down-regulation of Bcl-2 and generation of ROS

Mol Cancer Ther. 2003 Nov;2(11):1165-70.


C-phycocyanin, which is a major biliprotein of the blue-green algae, has been shown to possess cyclooxygenase-2 inhibitory activity. We have studied the effect of phycocyanin on a rat histiocytic tumor line. AK-5 cells are induced into apoptotic death program when treated with phycocyanin, which involves the activation of caspase-3. Phycocyanin-mediated apoptotic death is induced through the generation of reactive oxygen radicals. Free radical scavengers inhibited phycocyanin-induced apoptotic death in AK-5 cells. Bcl-2, an inhibitor of apoptosis, is shown to regulate ROS generation. Bcl-2 gene-transfected AK-5 cells are resistant to phycocyanin-induced death. Overexpression of Bcl-2 inhibited the production of ROS in phycocyanin-treated AK-5 cells. Thus, our observations demonstrate phycocyanin-induced apoptotic death in AK-5 cells, which is inhibited by Bcl-2 expression through the regulation of free radical generation. Phycocyanin, a natural product, could therefore be a possible chemotherapeutic agent through its apoptotic activity against tumor cells.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cyanobacteria
  • Cyclooxygenase 2
  • DNA Fragmentation / drug effects
  • Down-Regulation / drug effects
  • Isoenzymes / metabolism
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Phycocyanin / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Isoenzymes
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Phycocyanin
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases