Solanum lyratum Extracts Induce Extrinsic and Intrinsic Pathways of Apoptosis in WEHI-3 Murine Leukemia Cells and Inhibit Allograft Tumor. (7th May 2012)

• Record Type: Journal Article
• Authors: Yang, Jai-Sing; Wu, Chia-Chun; Kuo, Chao-Lin; Lan, Yu-Hsuan; Yeh, Chin-Chung; Yu, Chien-Chih; Lien, Jin-Cherng; Hsu, Yuan-Man; Kuo, Wei-Wen; Wood, W. Gibson; Tsuzuki, Minoru; Chung, Jing-Gung
• Other Names: Ramachandran Cheppail Academic Editor.
• Is Part Of: Evidence-based complementary and alternative medicine. Volume 2012(2012)
• Publication Date: 2012-05-07
• Subjects: Alternative medicine -- Periodicals; 615.505
• DOI: 10.1155/2012/254960
• Languages: English
• ISSNs: 1741-427X

Abstract

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 (Δ Ψ 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.