Evaluating skin cancer chemopreventive potential of water extract of Syzygium samarangense leaves through activation of the Nrf2-mediated cellular defense system

Oxidative stress has been demonstrated to cause gene mutations which may increase the morbidity of cancer; however, many phytochemicals may increase cellular antioxidant capacity for cancer chemoprevention in humans. Here, we evaluated skin cancer chemopreventive potential of Syzygium samarangense (wax apple) leaf water extract (WAL-WE) by activating Nrf2-mediated cellular antioxidant system. The results showed that WAL-WE at 100 and 250 μg/mL exhibited Nrf2-ARE pathway induction in the human HepG2-C8 cells with stably transfected ARE-luciferase plasmids. WAL-WE (0.25–2.0 μg/mL) also effectively inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse epidermal JB6 P+ cell transformation. WAL-WE increased mRNA and protein expressions of Nrf2 and Nrf2 downstream antioxidant and detoxification enzymes, such as HO-1, NQO1, and UGT1A, in HepG2-C8 and JB6 P+ cells. Moreover, WAL-WE was fractionated into 25 parts by applying a silica gel column chromatography. Among them, fraction 15 (eluted by ethyl acetate/methanol = 80:20) with higher yield showed the best Nrf2-ARE induction in HepG2-C8 cells, but the active components are needed to be further elucidated. These results suggest that WAL-WE may be a potential skin cancer chemopreventive agent through activation of the Nrf2 cellular defense pathway.