Solanum lyratumExtracts Induce Extrinsic and Intrinsic Pathways of Apoptosis in WEHI-3 Murine Leukemia Cells and Inhibit Allograft Tumor
Open Access
- 7 May 2012
- journal article
- research article
- Published by Hindawi Limited in Evidence-Based Complementary and Alternative Medicine
- Vol. 2012, 1-13
- https://doi.org/10.1155/2012/254960
Abstract
We investigated the molecular mechanisms of cell cycle arrest and apoptotic death induced bySolanum lyratumextracts (SLE) or diosgenin in WEHI-3 murine leukemia cellsin vitroand antitumor activityin vivo. Diosgenin is one of the components of SLE. Our study showed that SLE and diosgenin decreased the viable WEHI-3 cells and inducedphase 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. Thein vivostudy demonstrated that SLE has marked antitumor efficacy against tumors in the WEHI-3 cell allograft model. In conclusion, SLE- and diosgenin-inducedphase arrest and triggered extrinsic and intrinsic apoptotic pathways via p53 activation in WEHI-3 cells. SLE also exhibited antitumor activityin vivo. Our findings showed that SLE may be potentially efficacious in the treatment of leukemia in the future.
Funding Information
- National Science Council (NSC 97?2320-B-039-004-MY3, DOH101-TD-C-111-005, CMU96-086, CMU96-087)
This publication has 56 references indexed in Scilit:
- Targeting zebrafish and murine pituitary corticotroph tumors with a cyclin-dependent kinase (CDK) inhibitorProceedings of the National Academy of Sciences of the United States of America, 2011
- Rutin inhibits human leukemia tumor growth in a murine xenograft model in vivoEnvironmental Toxicology and Water Quality, 2011
- Ocimum gratissimumAqueous Extract Protects H9c2 Myocardiac Cells from H2O2-Induced Cell Apoptosis through Akt SignallingEvidence-Based Complementary and Alternative Medicine, 2010
- The Chemopreventive Effects of Protandim: Modulation of p53 Mitochondrial Translocation and Apoptosis during Skin CarcinogenesisPLOS ONE, 2010
- Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cellsMolecular Nutrition & Food Research, 2010
- The synthesized 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one (CHM-1) promoted G2/M arrest through inhibition of CDK1 and induced apoptosis through the mitochondrial-dependent pathway in CT-26 murine colorectal adenocarcinoma cellsThe Esophagus, 2009
- Diosgenin targets Akt‐mediated prosurvival signaling in human breast cancer cellsInternational Journal of Cancer, 2009
- Apoptotic myocytes generate monocyte chemoattractant protein-1 and mediate macrophage recruitmentJournal of Applied Physiology, 2008
- Twenty years of p53 research: structural and functional aspects of the p53 proteinOncogene, 1999
- Flow cytometric comparison of the effects of trialkyltins on the murine erythroleukemic cellToxicology, 1989