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Evidence-Based Complementary and Alternative Medicine
Volume 2012, Article ID 254960, 13 pages
http://dx.doi.org/10.1155/2012/254960
Research Article

Solanum lyratum Extracts Induce Extrinsic and Intrinsic Pathways of Apoptosis in WEHI-3 Murine Leukemia Cells and Inhibit Allograft Tumor

1Department of Pharmacology, China Medical University, Taichung 404, Taiwan
2Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan
3School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan
4School of Pharmacy, China Medical University, Taichung 404, Taiwan
5Department of Urology, China Medical University Hospital, Taichung 404, Taiwan
6Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 404, Taiwan
7Department of Pharmacology, School of Medicine, Geriatric Research, Education and Clinical Center, VA Medical Center, University of Minnesota, Minneapolis, MN 55455, USA
8Department of Biochemistry, Nihon Pharmaceutical University, Saitama 362-0806, Japan
9Tsuzuki Institute for Traditional Medicine, China Medical University, Taichung 404, Taiwan
10Department of Biotechnology, Asia University, Taichung 413, Taiwan

Received 28 September 2011; Revised 8 January 2012; Accepted 16 February 2012

Academic Editor: Cheppail Ramachandran

Copyright © 2012 Jai-Sing Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 phase arrest and apoptosis in concentration- or time-dependent manners. Both reagents increased the levels of ROS production and decreased the mitochondrial membrane potential ( ). 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 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.