Alteration of mitochondrial membrane potential by <i>Spirulina platensis</i> C‐phycocyanin induces apoptosis in the doxorubicinresistant human hepatocellular‐carcinoma cell line HepG2

Abstract

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 μM 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 μM 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.