Aminoguanidine induced apoptosis in human hepatocarcinoma HepG2 cells

Background: Aminoguanidine (AG, Pimagedine (R)) is an inhibitor of inducible nitric oxide synthase and diamine oxidase that inhibits tumor growth and has antioxidant effects. This study aimed to investigate the pro-apoptotic potentials of AG against human hepatocellular carcinoma cell line (HepG2). Methods: The effect of AG (0, 10, 30, and 40 mM) on cell death was evaluated by flow cytometry using AnnexinV/PI double staining in HepG2 cell line after 24 h. The expression of bax and bcl-2 genes was examined by Real Time PCR in HepG2 cells. Total NOx concentration was also measured according to Griess's reaction. Results: The results showed a dose-dependent apoptosis following treatment with AG and necrosis at the concentration higher than 40 mM in HepG2 cells. The bax/bcl-2 ratios were also dose-dependently increased in response to AG while NOx concentration decreased. Conclusion: The data suggest that the cytotoxicity of AG on HepG2 cells could be attributed to the induction of mitochondrial-dependent apoptosis through elevation of bax/bcl-2 gene expression ratio.