Dataset Information

Pharmacological inhibition of caspase-8 limits lung tumour outgrowth.

ABSTRACT:

Background and purpose

Lung cancer is one of the leading causes of cancer death worldwide. Despite advances in therapy, conventional therapy is still the main treatment and has a high risk of chemotherapy resistance. Caspase-8 is involved in cell death and is a recognized marker for poor patient prognosis.

Experimental approach

To elucidate the role of caspase-8 in lung carcinoma, we used human samples of non-small cell lung cancer (NSCLC) and a mouse model of carcinogen-induced lung cancer.

Key results

Healthy and cancerous NSCLC samples had similar levels of the active form of caspase-8. Similarly, lung tumour-bearing mice had high levels of the active form of caspase-8. Pharmacological inhibition of caspase-8 by z-IETD-FMK robustly reduced tumour outgrowth and this was closely associated with a reduction in the release of pro-inflammatory cytokines, IL-6, TNF-?, IL-18, IL-1?, IL-33, but not IL-1?. Furthermore, inhibition of caspase-8 reduced the recruitment of innate suppressive cells, such as myeloid-derived suppressor cells, but not of regulatory T cells to lungs of tumour-bearing mice. However, despite the well-known role of caspase-8 in cell death, the apoptotic cascade (caspase-3, caspase-9 and Bcl-2 dependent) was not active in lungs of z-IETD-treated tumour-bearing mice, but instead higher levels of the short segment of c-FLIP (c-FLIPs) were detected. Similarly, human healthy lung samples had higher levels of c-FLIPs than cancerous samples.

Conclusions and implications

Our data suggest that caspase-8 is an important orchestrator of cancer-associated inflammation and the presence of short segment of c-FLIP determines whether caspase-8 induces tumour proliferation or tumour arrest/regression in the lung.

SUBMITTER: Terlizzi M

PROVIDER: S-EPMC4523345 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Publications

Pharmacological inhibition of caspase-8 limits lung tumour outgrowth.

Terlizzi Michela M Di Crescenzo Vincenzo Giuseppe VG Perillo Giuseppe G Galderisi Antonio A Pinto Aldo A Sorrentino Rosalinda R

British journal of pharmacology 20150612 15

<h4>Background and purpose</h4>Lung cancer is one of the leading causes of cancer death worldwide. Despite advances in therapy, conventional therapy is still the main treatment and has a high risk of chemotherapy resistance. Caspase-8 is involved in cell death and is a recognized marker for poor patient prognosis.<h4>Experimental approach</h4>To elucidate the role of caspase-8 in lung carcinoma, we used human samples of non-small cell lung cancer (NSCLC) and a mouse model of carcinogen-induced l ...[more]

PMID: 25917370

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Dataset Information

Pharmacological inhibition of caspase-8 limits lung tumour outgrowth.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

Pharmacological inhibition of caspase-8 limits lung tumour outgrowth.

Similar Datasets

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