Antitumor effects of deguelin on H460 human lung cancer cells in vitro and in vivo: Roles of apoptotic cell death and H460 tumor xenografts model. Issue 1 (23rd November 2015)

• Record Type: Journal Article
• Authors: Hsu, Yu‐Chieh; Chiang, Jo‐Hua; Yu, Chun‐Shu; Hsia, Te‐Chun; Wu, Rick Sai‐Chuen; Lien, Jin‐Cherng; Lai, Kuang‐Chi; Yu, Fu‐Shun; Chung, Jing‐Gung
• Is Part Of: Environmental toxicology. Volume 32:Issue 1(2017)
• Page Start: 84
• Page End: 98
• Publication Date: 2015-11-23
• Subjects: deguelin -- H460 human lung cancer cells -- apoptosis -- mitochondria dysfunction -- xenograft tumor; Water quality bioassay -- Periodicals; Water -- Pollution -- Toxicology -- Periodicals; Microbiological assay -- Periodicals; Toxicity testing -- Periodicals; Environmental toxicology -- Periodicals; Environmental Pollution -- Periodicals; Environmental Pollutants -- Periodicals; Environmental Monitoring -- Periodicals; Écotoxicologie -- Périodiques; Pollution -- Périodiques; 615.902
• DOI: 10.1002/tox.22214
• Languages: English
• ISSNs: 1520-4081

Abstract

ABSTRACT: Deguelin, a naturally occurring rotenoid of the flavonoid family, is known to be an Akt inhibitor, to have chemopreventive activities and anti‐tumor effect on several cancers. In this study, investigation to elucidate the effect of deguelin on apoptotic pathways in human lung cancer cells and on the anti‐tumor effect in lung cancer xenograft nu/nu mice was performed. In vitro studies, found that deguelin induced cell morphological changes, and decreased the percentage of viability through the induction of apoptosis in H460 lung cancer cells. Deguelin triggered apoptosis in H460 cells was also confirmed by DAPI staining, DNA gel electrophoresis, and Annexin V‐FITC staining and these effects are dose‐dependent manners. It was also found that deguelin promoted the Ca 2+ production and activation of caspase‐3 but decreased the level of Δ Ψ m in H460 cells. Western blots indicated that the protein levels of cytochrome c, AIF, and pro‐apoptotic Bax and Bak protein were increased, but the anti‐apoptotic Bcl‐2 and Bcl‐x were decreased that may have led to apoptosis in H460 cells after exposure to deguelin. It was also confirmed by confocal laser microscope examination that deguelin promoted the release of AIF from mitochondria to cytosol. In vivo studies, found that in immunodeficient nu/nu mice bearing H460 tumor xenografts showed that the deguelin significantly suppressed tumor growth. Deguelin might be a potential therapeutic agent for the treatment of lung cancer in the future. This finding might fully support a critical event for deguelin via induction of apoptotic cell death and H460 tumor xenografts model against human lung cancer. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 84–98, 2017.