Dexamethasone inhibits TRAIL-induced apoptosis of thyroid cancer cells via Bcl-xL induction. 2006

Antonello Petrella, and Simona Francesca Ercolino, and Michela Festa, and Antonio Gentilella, and Alessandra Tosco, and Suzanne D Conzen, and Luca Parente
Department of Pharmaceutical Sciences, University of Salerno, Via Ponte Don Melillo, 84084 Fisciano, Salerno, Italy.

We have investigated the effect of dexamethasone (DEX) on the apoptosis induced by TRAIL (tumour necrosis factor-related apoptosis inducing ligand) in follicular undifferentiated thyroid (FRO) cancer cells. Apoptosis was measured by percent hypodiploid nuclei, caspase-3 and -8 activation, and mitochondrial membrane depolarisation. DEX nearly abolished TRAIL-induced apoptosis. The DEX protective effect was reverted by the steroid receptor antagonist RU486 suggesting that the DEX action is mediated by glucocorticoid receptor (GR) activation. The role of Bcl proteins in the DEX effect was then investigated. In FRO cells DEX stimulated in a time-dependent fashion the expression of Bcl-xL, but not that of Bcl-2, Bax and Bad. In addition, Bcl-xL mRNA was significantly increased in the presence of DEX, suggesting a transcriptional regulation by the steroid. Transfection of the cells with siRNAs against Bcl-xL inhibited both basal and DEX-stimulated Bcl-xL expression and restored apoptosis in TRAIL-stimulated cells treated with DEX. These results demonstrate that dexamethasone protects thyroid cancer cells from apoptosis induced by TRAIL. DEX acts via GR activation and up-regulation of the expression of the anti-apoptotic protein Bcl-xL.

UI MeSH Term Description Entries
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D013964 Thyroid Neoplasms Tumors or cancer of the THYROID GLAND. Cancer of Thyroid,Thyroid Cancer,Cancer of the Thyroid,Neoplasms, Thyroid,Thyroid Adenoma,Thyroid Carcinoma,Adenoma, Thyroid,Adenomas, Thyroid,Cancer, Thyroid,Cancers, Thyroid,Carcinoma, Thyroid,Carcinomas, Thyroid,Neoplasm, Thyroid,Thyroid Adenomas,Thyroid Cancers,Thyroid Carcinomas,Thyroid Neoplasm
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D051020 bcl-X Protein A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS and is a regulatory subunit for PROTEIN PHOSPHATASE 1. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL. bcl-XL Protein,bcl-XS Protein,bcl-X(L) Protein,bcl-X(S) Protein,bcl-Xa Protein,bcl-Xalpha Protein,bcl-Xb Protein,bcl-Xbeta Protein,bcl-Xlong Protein,bcl-Xshort Protein,bcl-x(beta) Protein,bcl2-Like 1 Protein,bcl2L1 Protein,bcl X Protein,bcl XL Protein,bcl XS Protein,bcl Xa Protein,bcl Xalpha Protein,bcl Xb Protein,bcl Xbeta Protein,bcl Xlong Protein,bcl Xshort Protein,bcl2 Like 1 Protein
D053221 TNF-Related Apoptosis-Inducing Ligand A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form. Tumor Necrosis Factor Ligand Superfamily Member 10,Apo-2 Ligand,Apo-2L Protein,CD253 Antigen,TNF Superfamily, Member 10,TRAIL Protein,Antigen, CD253,Apo 2 Ligand,Apo 2L Protein,Apoptosis-Inducing Ligand, TNF-Related,TNF Related Apoptosis Inducing Ligand
D018265 Carcinoma, Papillary, Follicular A thyroid neoplasm of mixed papillary and follicular arrangement. Its biological behavior and prognosis is the same as that of a papillary adenocarcinoma of the thyroid. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1271)

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