, 2001). The hypothesis that the apoptotic cell death in a murine melanoma cell line is a consequence of the pro-oxidative action of G8 and G12 is supported by its ability to induce NF-κB, a factor that was characterized in previous studies ( Locatelli et al., 2009). Although the NF-κB activation may
promote the transcription of both anti- and proapoptotic proteins, it was reported that its activation occurs in pro-oxidant conditions ( Meyskens et al., 1999). In this way, it is possible to infer that the NF-κB induction by esters of gallic acid demonstrated in previous studies would be directly related to the induction of ROS generation by these compounds. Previously we have demonstrated the HOCl scavenging capability (Rosso et al., 2006) and cytotoxicity signaling pathway on B16F10 cells (Locatelli et al., 2009) of the gallic acid and 14 n-alkyl gallates, with the same number of hydroxyl substituents, varying only the side carbonic chain length. All tested gallates, regardless of their alkyl chain length, showed a potent scavenging activity. However, only four gallates showed cytotoxic effect to B16F10 cells, indicating that the alkyl chain length was not directly related to its antioxidant activity and that the cytotoxic activity depends on the alkyl
RG7422 in vivo chain length. The H-atom or electron transfer and metals chelation are the main mechanisms proposed in related studies on the antioxidant action of polyphenols. In respect to gallic acid, the excellent ROS scavenger action was suggested to be due to a hydrogen atom donation (Leopoldini et al., 2011). However, the development of pro-oxidative properties by phenolic antioxidants such as propyl gallate was also demonstrated, and it was suggested that it occurs due to redox reactions among metal ions and the phenolic compound (Aruoma et al., 1993, Jacobi et al., 1999, Kobayashi et al., 2004 and Rodtjer et al., 2006). Octyl gallate has been suggested to present both antioxidant
(Nakayama et al., 1993) and pro-oxidant properties (Roy et al., 2000) depending on its concentration Erythromycin and cellular conditions; considering that the antioxidant effect is related to higher concentrations of the compounds, probably due to the high ratio between the gallate and metal ions. This effect was demonstrated in an experiment in which low concentrations of propyl gallate, in combination with copper, induced lipid peroxidation in human fibroblasts (Jacobi et al., 1999). Moreover, in other study, low concentrations of aloin, one of the two main components of Aloe, exhibited pro-oxidant effect due its reducing activity on iron ions, which enhanced the generation of hydroxyl radicals by Fenton reaction. Otherwise, at higher concentrations, the free radical-scavenging activity of aloin gradually predominated over its reducing power, resulting in the protection of DNA (Tian and Hua, 2005).