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

Antonello Petrella; Simona Francesca Ercolino; Michela Festa; Antonio Gentilella; Alessandra Tosco; Suzanne D. Conzen; Luca Parente

doi:10.1016/j.ejca.2006.07.018

Dexamethasone inhibits TRAIL-induced apoptosis of thyroid cancer cells via Bcl-x_L induction

Antonello Petrella, Simona Francesca Ercolino, Michela Festa, Antonio Gentilella, Alessandra Tosco, Suzanne D. Conzen, Luca Parente

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

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-x_L, but not that of Bcl-2, Bax and Bad. In addition, Bcl-x_L mRNA was significantly increased in the presence of DEX, suggesting a transcriptional regulation by the steroid. Transfection of the cells with siRNAs against Bcl-x_L inhibited both basal and DEX-stimulated Bcl-x_L 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-x_L.

Original language	English (US)
Pages (from-to)	3287-3293
Number of pages	7
Journal	European Journal of Cancer
Volume	42
Issue number	18
DOIs	https://doi.org/10.1016/j.ejca.2006.07.018
State	Published - Dec 2006
Externally published	Yes

Keywords

Apoptosis
Bcl-2 proteins
Dexamethasone
TRAIL
Thyroid cancer

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1016/j.ejca.2006.07.018

Cite this

@article{ed48873acc744250ab98f230b2e20b6b,

title = "Dexamethasone inhibits TRAIL-induced apoptosis of thyroid cancer cells via Bcl-xL induction",

abstract = "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.",

keywords = "Apoptosis, Bcl-2 proteins, Dexamethasone, TRAIL, Thyroid cancer",

author = "Antonello Petrella and Ercolino, {Simona Francesca} and Michela Festa and Antonio Gentilella and Alessandra Tosco and Conzen, {Suzanne D.} and Luca Parente",

note = "Funding Information: This work was supported by grants from the University of Salerno (60% 2004, 2005) and from the Italian Ministry of Research (COFIN 2002) to L.P. S.F.E. and M.F. are supported by Fondo Sociale Europeo (PON 2000-06, Misura III.4).",

year = "2006",

month = dec,

doi = "10.1016/j.ejca.2006.07.018",

language = "English (US)",

volume = "42",

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journal = "European Journal of Cancer",

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TY - JOUR

T1 - Dexamethasone inhibits TRAIL-induced apoptosis of thyroid cancer cells via Bcl-xL induction

AU - Petrella, Antonello

AU - Ercolino, Simona Francesca

AU - Festa, Michela

AU - Gentilella, Antonio

AU - Tosco, Alessandra

AU - Conzen, Suzanne D.

AU - Parente, Luca

N1 - Funding Information: This work was supported by grants from the University of Salerno (60% 2004, 2005) and from the Italian Ministry of Research (COFIN 2002) to L.P. S.F.E. and M.F. are supported by Fondo Sociale Europeo (PON 2000-06, Misura III.4).

PY - 2006/12

Y1 - 2006/12

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Bcl-2 proteins

KW - Dexamethasone

KW - TRAIL

KW - Thyroid cancer

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