title: Anisomycin treatment enhances TRAIL-mediated apoptosis in renal carcinoma cells through the down-regulation of Bcl-2, c-FLIP(L) and Mcl-1.
abstract: Anisomycin is known to inhibit protein synthesis and induce ribotoxic stress. In this study, we investigated whether anisomycin treatment could modulate TRAIL-mediated apoptosis in human renal carcinoma Caki cells. We found that anisomycin treatment (10-15 nM) alone had no effect on the level of apoptosis, but a combination treatment of anisomycin and TRAIL significantly increased the level of apoptosis in human renal carcinoma (Caki, ACHN and A498), human glioma (U251MG), and human breast carcinoma (MDA-MB-361 and MCF7) cells. Anisomycin treatment led to the down-regulation of Bcl-2 expression at the transcriptional level, and the over-expression of Bcl-2 inhibited the apoptosis induced by the combination treatment of anisomycin and TRAIL. Furthermore, anisomycin treatment resulted in the down-regulation of c-FLIP(L) and Mcl-1 at the post-transcriptional level, and the over-expression of c-FLIP(L) and Mcl-1 blocked the induction of apoptosis caused by the combination treatment of anisomycin with TRAIL. In contrast, anisomycin treatment had no effect on the levels of TRAIL-mediated apoptosis in mouse kidney cells (TMCK-1) or normal human skin fibroblasts (HSF). Cumulatively, our study demonstrates that anisomycin treatment enhances TRAIL-mediated apoptosis through the down-regulation of Bcl-2, c-FLIP(L) and Mcl-1 at the transcriptional or post-transcriptional level.
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, South Korea.
authors.forename: Bo Ram
authors.initials: BR
authors.lastname: Seo
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Min
authors.forename: Shin
authors.initials: S
authors.lastname: Kim
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Park
authors.forename: Won-Kyun
authors.initials: WK
authors.lastname: Park
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Lee
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D051379:Mice; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; D000841:Anisomycin