Molecular mechanisms in C-Phycocyanin induced apoptosis in human chronic myeloid leukemia cell line-K562

Biochem Pharmacol. 2004 Aug 1;68(3):453-62. doi: 10.1016/j.bcp.2004.02.025.

Abstract

C-Phycocyanin (C-PC), the major light harvesting biliprotein from Spirulina platensis is of greater importance because of its various biological and pharmacological properties. It is a water soluble, non-toxic fluorescent protein pigment with potent anti-oxidant, anti-inflammatory and anti-cancer properties. In the present study the effect of highly purified C-PC was tested on growth and multiplication of human chronic myeloid leukemia cell line (K562). The results indicate significant decrease (49%) in the proliferation of K562 cells treated with 50 microM C-PC up to 48 h. Further studies involving fluorescence and electron microscope revealed characteristic apoptotic features like cell shrinkage, membrane blebbing and nuclear condensation. Agarose electrophoresis of genomic DNA of cells treated with C-PC showed fragmentation pattern typical for apoptotic cells. Flow cytometric analysis of cells treated with 25 and 50 microM C-PC for 48 h showed 14.11 and 20.93% cells in sub-G0/G1 phase, respectively. C-PC treatment of K562 cells also resulted in release of cytochrome c into the cytosol and poly(ADP) ribose polymerase (PARP) cleavage. These studies also showed down regulation of anti-apoptotic Bcl-2 but without any changes in pro-apoptotic Bax and thereby tilting the Bcl-2/Bax ratio towards apoptosis. These effects of C-PC appear to be mediated through entry of C-PC into the cytosol by an unknown mechanism. The present study thus demonstrates that C-PC induces apoptosis in K562 cells by cytochrome c release from mitochondria into the cytosol, PARP cleavage and down regulation of Bcl-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Cell Division / drug effects
  • Cytochromes c / metabolism
  • DNA Fragmentation / drug effects
  • Humans
  • Immunoblotting
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Phycocyanin / pharmacology*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • bcl-2-Associated X Protein

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Phycocyanin
  • Cytochromes c
  • Poly(ADP-ribose) Polymerases