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

• Published in: South African journal of botany Vol. 137; pp. 303 - 310
• Main Authors: Su, Zheng-Yuan, Chan, Yen-Fan, Tung, Yen-Chen, Sung, Ping-Hua, Chen, Pei-Chun, Lin, Zi-Han, Wu, Tien-Yuan
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.03.2021
• Subjects: Cancer chemoprevention; Cellular antioxidant ability; Nrf2; Silica gel column chromatography; Syzygium samarangense; Cancer chemoprevention; Cellular antioxidant ability; Silica gel column chromatography; Syzygium samarangense; Nrf2
• ISSN: 0254-6299; 1727-9321
• DOI: 10.1016/j.sajb.2020.10.029

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. [Display omitted] •Water extract of .S. samarangense leaf (WAL-WE) activates the Nrf2 pathway in human hepatoma HepG2-C8 cells stably transfected with ARE-luciferase reporter plasmids.•WAL-WE may effectively inhibited the TPA-stimulated neoplastic transformation of mouse epidermal JB6 P+ cells by activating Nrf2-mediated antioxidant enzymes.•A fraction eluted by ethyl acetate/methanol = 80:20, 5 L from WAL-WE by silica gel chromatography may be the main contributor to the activation of Nrf2 pathway.