Alteration of mitochondrial membrane potential by Spirulina platensis C-phycocyanin induces apoptosis in the doxorubicinresistant human hepatocellular-carcinoma cell line HepG2.
C-PC (C-phycocyanin) is a water-soluble biliprotein from the filamentous cyanobacterium Spirulina platensis with potent antioxidant, anti-inflammatory and anticancerous properties. In the present study, the effect of C-PC was tested on the proliferation of doxorubicin-sensitive (S-HepG2) and -resistant (R-HepG2) HCC (hepatocellular carcinoma) cell lines. These studies indicate a 50% decrease in the proliferation of S- and R-HepG2 cells treated with 40 and 50 microM C-PC for 24 h respectively. C-PC also enhanced the sensitivity of R-HepG2 cells to doxorubicin. R-HepG2 cells treated with C-PC showed typical apoptotic features such as membrane blebbing and DNA fragmentation. Flow-cytometric analysis of R-HepG2 cells treated with 10, 25 and 50 microM C-PC for 24 h showed 18.8, 39.72 and 65.64% cells in sub-G(0)/G(1)-phase respectively. Cytochrome c release, decrease in membrane potential, caspase 3 activation and PARP [poly(ADP-ribose) polymerase] cleavage were observed in C-PC-treated R-HepG2 cells. These studies also showed down-regulation of the anti-apoptotic protein Bcl-2 and up-regulation of the pro-apoptotic Bax (Bcl2-associated X-protein) protein in the R-HepG2 cells treated with C-PC. The present study thus demonstrates that C-PC induces apoptosis in R-HepG2 cells and its potential as an anti-HCC agent.
Roy
Karnati R
KR
Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad, India.
Arunasree
Kalle M
KM
Reddy
Nishant P
NP
Dheeraj
Bhavanasi
B
Reddy
Gorla Venkateswara
GV
Reddanna
Pallu
P
D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000503:physiopathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D010798:Phycocyanin / Q000008:administration & dosage*; D053545:Spirulina / Q000378:metabolism*
D010798:Phycocyanin; D004317:Doxorubicin