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

In the apoptotic process, there are two different types of cell death: caspase-dependent and caspase-independent pathways. In As-induced apoptosis, involvement of caspase-3 activation has been well known in both in vivo and in vitro experimental systems (32, 33) . In this study, we found that the cytoprotective effect of licorice against As-induced cell death was mediated by the inhibition of apoptisis. Licorice inhibited caspase-3 activation (Fig. 6 ) and reduced the population of apoptotic cells (Fig. 4) in a dose dependent manner. In Fig. 6 , caspase-3 activation was inhibited by both 0.1 and 1.0 mg ml À1 of licorice to a similar extent. However, the net cell viability by 1.0 mg ml À1 of licorice was much higher than that by 0.1 mg ml À1 of licorice (Fig. 3) indicating the role of caspase-independent apoptotic pathways in this cell line. Apoptosis inducing factor (AIF) and endonuclease G (EndoG) are apoptogenic factors that mediate caspase-independent cell death (34, 35) . Omi/HtrA2 also induces caspase-independent apoptosis by inhibiting IAPs (inhibitors of apoptosis) for activating caspase-9 and -3 (35) . To confirm apoptosis through the caspase-independent pathways including EndoG-induced DNA degradation, further studies are needed. In summary, we demonstrated that licorice blocked As-induced cell death by inhibiting the apoptotic process, and suggested that licorice is a potent preventer of As-induced cytotoxicity.