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Reduction of the antiapoptotic protein cFLIP enhances the susceptibility of human renal cancer cells to TRAIL apoptosis.
Cancer Immunol Immunother. 2005 May; 54(5):499-505.CI

Abstract

Human renal carcinoma cells (RCCs) were sensitized to the apoptotic effects of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), by treatment with cycloheximide (CHX). In contrast to a previous study, a rapid and dramatic decrease in levels of cellular FLICE (Fas-associated death domain-like IL-1beta-converting enzyme) inhibitory protein (cFLIP) following cycloheximide treatment was observed in all RCCs studied. The unambiguous detection of this decrease in cFLIP was dependent on the quality of the particular antibody preparation used to detect cFLIP. Cycloheximide treatment caused no major change in levels of pro-caspase-8 or cell surface expression of TRAIL receptors. Therefore, cycloheximide treatment resulted in an increase in the pro-caspase-8 to cFLIP ratio, which correlated with sensitization to TRAIL-mediated apoptosis. Furthermore, treatment of human RCCs with small interfering oligoribonucleotides (siRNA) for cFLIP caused a reduction of cFLIP protein and sensitized cells to TRAIL-mediated apoptosis. We concluded that in the presence of an intact TRAIL signaling pathway, a significant reduction of cFLIP alone is sufficient to sensitize human RCCs to TRAIL apoptosis.

Authors+Show Affiliations

SAIC-Frederick, National Cancer Institute at Frederick, Bldg. 560, Rm. 31-67, Frederick, MD 21702-1201, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15614529

Citation

Brooks, Alan D., and Thomas J. Sayers. "Reduction of the Antiapoptotic Protein cFLIP Enhances the Susceptibility of Human Renal Cancer Cells to TRAIL Apoptosis." Cancer Immunology, Immunotherapy : CII, vol. 54, no. 5, 2005, pp. 499-505.
Brooks AD, Sayers TJ. Reduction of the antiapoptotic protein cFLIP enhances the susceptibility of human renal cancer cells to TRAIL apoptosis. Cancer Immunol Immunother. 2005;54(5):499-505.
Brooks, A. D., & Sayers, T. J. (2005). Reduction of the antiapoptotic protein cFLIP enhances the susceptibility of human renal cancer cells to TRAIL apoptosis. Cancer Immunology, Immunotherapy : CII, 54(5), 499-505.
Brooks AD, Sayers TJ. Reduction of the Antiapoptotic Protein cFLIP Enhances the Susceptibility of Human Renal Cancer Cells to TRAIL Apoptosis. Cancer Immunol Immunother. 2005;54(5):499-505. PubMed PMID: 15614529.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduction of the antiapoptotic protein cFLIP enhances the susceptibility of human renal cancer cells to TRAIL apoptosis. AU - Brooks,Alan D, AU - Sayers,Thomas J, Y1 - 2004/12/22/ PY - 2004/06/02/received PY - 2004/07/06/accepted PY - 2004/12/23/pubmed PY - 2005/5/12/medline PY - 2004/12/23/entrez SP - 499 EP - 505 JF - Cancer immunology, immunotherapy : CII JO - Cancer Immunol Immunother VL - 54 IS - 5 N2 - Human renal carcinoma cells (RCCs) were sensitized to the apoptotic effects of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), by treatment with cycloheximide (CHX). In contrast to a previous study, a rapid and dramatic decrease in levels of cellular FLICE (Fas-associated death domain-like IL-1beta-converting enzyme) inhibitory protein (cFLIP) following cycloheximide treatment was observed in all RCCs studied. The unambiguous detection of this decrease in cFLIP was dependent on the quality of the particular antibody preparation used to detect cFLIP. Cycloheximide treatment caused no major change in levels of pro-caspase-8 or cell surface expression of TRAIL receptors. Therefore, cycloheximide treatment resulted in an increase in the pro-caspase-8 to cFLIP ratio, which correlated with sensitization to TRAIL-mediated apoptosis. Furthermore, treatment of human RCCs with small interfering oligoribonucleotides (siRNA) for cFLIP caused a reduction of cFLIP protein and sensitized cells to TRAIL-mediated apoptosis. We concluded that in the presence of an intact TRAIL signaling pathway, a significant reduction of cFLIP alone is sufficient to sensitize human RCCs to TRAIL apoptosis. SN - 0340-7004 UR - https://www.unboundmedicine.com/medline/citation/15614529/Reduction_of_the_antiapoptotic_protein_cFLIP_enhances_the_susceptibility_of_human_renal_cancer_cells_to_TRAIL_apoptosis_ L2 - https://dx.doi.org/10.1007/s00262-004-0595-8 DB - PRIME DP - Unbound Medicine ER -