title: 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.
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 Ca2+production and activation of caspase-3 but decreased the level of ΔΨmin 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.
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Hsu
authors.affiliation: Department of Nursing, Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi County, 62241, Taiwan.
authors.forename: Jo-Hua
authors.initials: JH
authors.lastname: Chiang
authors.affiliation: School of Pharmacy, China Medical University, Taichung, 404, Taiwan.
authors.forename: Chun-Shu
authors.initials: CS
authors.lastname: Yu
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.|Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Te-Chun
authors.initials: TC
authors.lastname: Hsia
authors.affiliation: Department of Anesthesiology, China Medical University Hospital, Taichung, 404, Taiwan.
authors.forename: Rick Sai-Chuen
authors.initials: RS
authors.lastname: Wu
authors.affiliation: School of Pharmacy, China Medical University, Taichung, 404, Taiwan.
authors.forename: Jin-Cherng
authors.initials: JC
authors.lastname: Lien
authors.affiliation: School of Medicine, China Medical University Hospital, Taichung, 404, Taiwan.|Department of Surgery, China Medical University Beigang Hospital, Yunlin, 651, Taiwan.
authors.forename: Kuang-Chi
authors.initials: KC
authors.lastname: Lai
authors.affiliation: School of Dentist, China Medical University, Taichung, 404, Taiwan.
authors.forename: Fu-Shun
authors.initials: FS
authors.lastname: Yu
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.|Department of Biotechnology, Asia University, Taichung, 413, Taiwan.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012402:Rotenone / Q000031:analogs & derivatives* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D016588:Anticarcinogenic Agents; D051017:Apoptosis Regulatory Proteins; D012402:Rotenone; C505409:Casp3 protein, mouse; D053148:Caspase 3; C107676:deguelin; D002118:Calcium
keywords: H460 human lung cancer cells; apoptosis; deguelin; mitochondria dysfunction; xenograft tumor