title: Osthole enhances TRAIL-mediated apoptosis through downregulation of c-FLIP expression in renal carcinoma Caki cells.
abstract: Osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, has been shown to induce various beneficial biochemical effects such as anti-inflammatory and antitumor. In the present study, we examined whether osthole could sensitize TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human renal carcinoma Caki cells. We found that osthole and TRAIL alone, had no effect on apoptosis, but combined treatment with osthole and TRAIL markedly induced apoptosis in Caki (renal carcinoma), U251MG (glioma) and MDA-MB-231 (breast carcinoma) cells. In contrast, combined treatment with osthole and TRAIL did not induce apoptosis in normal human skin fibroblast cells. Osthole induced downregulation of cellular FLICE-like inhibitory protein (c-FLIP) expression, and overexpression of c-FLIP markedly blocked apoptosis induced by the combined treatment with osthole and TRAIL. In addition, osthole markedly reduced mitochondrial membrane potential levels, and increased cytosolic cytochrome c release in combined treatment with osthole and TRAIL. Therefore, these data suggest that osthole may be an efficient TRAIL sensitizer.
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Min
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Min Ae
authors.initials: MA
authors.lastname: Han
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Shin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
mesh_terms: D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D015536:Down-Regulation; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D003374:Coumarins; D053221:TNF-Related Apoptosis-Inducing Ligand; C046627:osthol