Abstract
BackgroundAminoguanidine (AG, Pimagedine®) 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). MethodsThe effect of AG (0, 10, 30, and 40 mM) on cell death was evaluated by flow cytometry using Annexin-V/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. ResultsThe 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. ConclusionThe 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.
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