title: Peroxisome proliferator-activated receptor γ ligand troglitazone and TRAIL synergistically induce apoptosis.
abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to cause apoptosis in several types of malignant tumor cells through its interaction with the death domain-containing receptor, death receptor 5 (DR5). In the present study, we showed that co-treatment with troglitazone (TGZ), a synthetic ligand of peroxisome proliferator-activated receptor γ (PPARγ), and TRAIL synergistically induced apoptosis through DR5 upregulation in human colon cancer DLD-1 cells. TGZ elevated DR5 expression at the promoter level through the CCAAT/enhancer-binding protein homologous protein (CHOP) binding site. These results suggest that combined treatment with TGZ and TRAIL may be promising as a new therapy against malignant tumors.
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Koyama
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sowa
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Mano
authors.initials: M
authors.lastname: Horinaka
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Ahmed E
authors.initials: AE
authors.lastname: Goda
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Fujiwara
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakai
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000473:pathology; D004357:Drug Synergism; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D006801:Humans; D047495:PPAR gamma; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000077288:Troglitazone
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D002839:Chromans; C497249:DDIT3 protein, human; D047495:PPAR gamma; D034741:RNA, Small Interfering; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D045162:Thiazolidinediones; D051742:Transcription Factor CHOP; D000077288:Troglitazone