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

• Published in: Biochemical pharmacology Vol. 68; no. 3; pp. 453 - 462
• Main Authors: Subhashini, Jagu, Mahipal, Suraneni V.K, Reddy, Madhava C, Mallikarjuna Reddy, Metukuri, Rachamallu, Aparna, Reddanna, Pallu
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2004; Elsevier Science
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis; Bcl-2; bcl-2-Associated X Protein; Biological and medical sciences; C-PC; Cell Division - drug effects; Cytochrome c; Cytochromes c - metabolism; DNA Fragmentation - drug effects; Humans; Immunoblotting; K562 Cells; K562 human chronic myeloid leukemia cell line; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Medical sciences; PARP; Pharmacology. Drug treatments; Phycocyanin - pharmacology; Poly(ADP-ribose) Polymerases - metabolism; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Cytochrome c; Bcl-2; C-PC; CML; K562 human chronic myeloid leukemia cell line; PARP; FACS; COX; Apoptosis; Human; Malignant hemopathy; Pharmacology; Myeloproliferative syndrome; Chronic; Cell death; Chronic myelocytic leukemia; Mechanism of action
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2004.02.025

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 μM 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 μM 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.