Abstract | BACKGROUND: METHODS: We examined the response of a panel of nine HNSCC cell lines to TRAIL and SMs and investigated the mechanism of cell type-specific response by functional analysis. RESULTS:
Head and neck cancer cell lines revealed a converse response pattern with three cell lines being highly sensitive to Smac-164 (SM) but resistant to TRAIL, whereas the other six were sensitive to TRAIL but resistant to SM. Distinct protein expression and activation patterns were found to be associated with susceptibility of HNSCC cell lines to TRAIL and SM. Tumour necrosis factor-related apoptosis-inducing ligand sensitivity was associated with high caspase-8 and Bid protein levels, and TRAIL-sensitive cell lines were killed via the type II extrinsic apoptotic pathway. Smac mimetic-sensitive cells expressed low levels of caspase-8 and Bid but had high TNF-α expression. Smac mimetic-induced cell death was associated with caspase-10 activation, suggesting that in the absence of caspase-8, caspase-10 mediates response to SM. Cotreatment with TNF-α sensitised the resistant cells to SM, demonstrating a decisive role for TNF-α-driven feedback loop in SM sensitivity. CONCLUSIONS:
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Authors | N Raulf, R El-Attar, D Kulms, D Lecis, D Delia, H Walczak, K Papenfuss, E Odell, M Tavassoli |
Journal | British journal of cancer
(Br J Cancer)
Vol. 111
Issue 10
Pg. 1955-64
(Nov 11 2014)
ISSN: 1532-1827 [Electronic] England |
PMID | 25314064
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- BH3 Interacting Domain Death Agonist Protein
- Bridged Bicyclo Compounds, Heterocyclic
- SM 164
- TNF-Related Apoptosis-Inducing Ligand
- Triazoles
- Tumor Necrosis Factor-alpha
- Caspase 10
- Caspase 8
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Topics |
- Apoptosis
(drug effects)
- BH3 Interacting Domain Death Agonist Protein
(metabolism)
- Biomimetics
- Blotting, Western
- Bridged Bicyclo Compounds, Heterocyclic
(pharmacology)
- Carcinoma, Squamous Cell
(drug therapy, metabolism, pathology)
- Caspase 10
(metabolism)
- Caspase 8
(metabolism)
- Cell Proliferation
(drug effects)
- Enzyme-Linked Immunosorbent Assay
- Head and Neck Neoplasms
(drug therapy, metabolism, pathology)
- Humans
- TNF-Related Apoptosis-Inducing Ligand
(pharmacology)
- Triazoles
(pharmacology)
- Tumor Cells, Cultured
- Tumor Necrosis Factor-alpha
(metabolism)
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