Cytoprotective Activity of Glycyrrhizae radix Extract Against Arsenite-induced Cytotoxicity

Kim, Sang Chan; Park, Sook Jahr; Lee, Jong Rok; Seo, Jung Cheol; Yang, Chae Ha; Byun, Sung Hui

A previous study from our laboratory showed that licorice prevented Cd-induced toxicity in H4IIE cells (3) . Thus, we are interested in whether or not licorice protects against As toxicity in H4IIE cells. In the present study, licorice significantly inhibited As-induced cell death. As-induced either apoptosis at lower concentration or necrosis at high concentration in mouse embryonic fibroblasts (28) , human osteogenic sarcoma cell line U-2OS (29) and human leukemia HL-60 cells (30) . Previously, Son et al. (31) determined that the sulfur amino acid deprivation (SAAD) potentiated the cytotoxicity of As by 20-fold in H4IIE cells. Although SAAD potentiated cytotoxicity of H4IIE cells with IC 50 value of 19 uM, the IC 50 value of As in H4IIE cells incubated in control medium was 401 uM. It is consistent with our results showing about 50% of cytotoxicity by 400 uM of As in H4IIE cells. Figure 5 . DNA Laddering of H4IIE cells exposed to As with/without licorice. H4IIE cells that had been pre-treated with licorice for 12 h were further incubated with licorice þ As (400 mM) for another 12 h. To determine whether As induces apoptotic cell death, we analyzed cell death using a flow cytometer. Incubation with As produced apoptotic cell death, but this As-induced apoptotic cell death was significantly prevented by 1.0 mg ml À1 of licorice. These results present strong evidence that licorice's potent blocking of cell death is due to its inhibitory effect on As-mediated apoptotic process. As-induced apoptosis was confirmed by data that licorice inhibits As-induced DNA laddering.