FAM83G-based Peptide Induces Apoptosis on Cultured Liver Cancer Cell

Abstract

Background: Previously, AF-956, which contains S356 of FAM83G and an N-terminal antenna peptide for entry into colon cancer cells, is markedly antiproliferative compared to a control peptide (AF-859), which lacks the N-terminal antenna peptide, by inducing apoptosis via the inhibition of HSP27 phosphorylation at residues S15 and S82.

Objective: Because FAM83G-derived peptides are promising lead compounds for colon cancer treatment, we reanalyzed the effect of AG-066, which contains S356 of FAM83G and an N-terminal antenna peptide for entry into the liver cancer cells.

Methods: HepG2 liver cancer cells were incubated with either AF-859 or AG-066 at a concentration of 54 μM at 37 °C for 24, 48, and 72 h. The effects of AF-859 and AG-066 on the cultured HepG2 cells were estimated using an inverted light microscope. Furthermore, the DNA ladder method and the dead cell assay were performed by applying Live/Dead Cell Staining Kit II. Erk phosphorylation was estimated by western blotting.

Results: Treatment with AG-066 markedly reduced HepG2 viable cell counts compared to the AF- 859-treated HepG2 cells, as evident from the significantly increased number of dead cells in the culture medium. Additionally, AG-066 treatment increased cellular DNA laddering. We found no difference in Erk phosphorylation status between the AG-066- and AF-859-treated groups.

Conclusion: This study illustrated that the peptide with a structure based on FAM83G functions as a spontaneous apoptosis inducer for liver cancer cells. Hence, it is a promising lead compound for the treatment of liver cancer.

Keywords: DNA ladder; FAM83G; HepG2 cell; apoptosis; extracellular signal-regulated kinase; liver cancer cell.