title: Solanum lyratum Extracts Induce Extrinsic and Intrinsic Pathways of Apoptosis in WEHI-3 Murine Leukemia Cells and Inhibit Allograft Tumor.
abstract: We investigated the molecular mechanisms of cell cycle arrest and apoptotic death induced by Solanum lyratum extracts (SLE) or diosgenin in WEHI-3 murine leukemia cells in vitro and antitumor activity in vivo. Diosgenin is one of the components of SLE. Our study showed that SLE and diosgenin decreased the viable WEHI-3 cells and induced G(0)/G(1) phase arrest and apoptosis in concentration- or time-dependent manners. Both reagents increased the levels of ROS production and decreased the mitochondrial membrane potential (ΔΨ(m)). SLE- and diosgenin-triggered apoptosis is mediated through modulating the extrinsic and intrinsic signaling pathways. Intriguingly, the p53 inhibitor (pifithrin-α), anti-Fas ligand (FasL) mAb, and specific inhibitors of caspase-8 (z-IETD-fmk), caspase-9 (z-LEHD-fmk), and caspase-3 (z-DEVD-fmk) blocked SLE- and diosgenin-reduced cell viability of WEHI-3 cells. The in vivo study demonstrated that SLE has marked antitumor efficacy against tumors in the WEHI-3 cell allograft model. In conclusion, SLE- and diosgenin-induced G(0)/G(1) phase arrest and triggered extrinsic and intrinsic apoptotic pathways via p53 activation in WEHI-3 cells. SLE also exhibited antitumor activity in vivo. Our findings showed that SLE may be potentially efficacious in the treatment of leukemia in the future.
authors.affiliation: Department of Pharmacology, China Medical University, Taichung 404, Taiwan.
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Wu
authors.forename: Chao-Lin
authors.initials: CL
authors.lastname: Kuo
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Lan
authors.forename: Chin-Chung
authors.initials: CC
authors.lastname: Yeh
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Yu
authors.forename: Jin-Cherng
authors.initials: JC
authors.lastname: Lien
authors.forename: Yuan-Man
authors.initials: YM
authors.lastname: Hsu
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.forename: W Gibson
authors.initials: WG
authors.lastname: Wood
authors.forename: Minoru
authors.initials: M
authors.lastname: Tsuzuki
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung