TUCAN/CARDINAL/CARD8 and apoptosis resistance in non-small cell lung cancer cells
<p>Abstract</p> <p>Background</p> <p>Activation of caspase-9 in response to treatment with cytotoxic drugs is inhibited in NSCLC cells, which may contribute to the clinical resistance to chemotherapy shown in this type of tumor. The aim of the present study was to inves...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2006-06-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/6/166 |
| _version_ | 1811294514508201984 |
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| author | Ferreira Carlos G Hoogeland Bas SJ Giaccone Giuseppe Checinska Agnieszka Rodriguez Jose A Kruyt Frank AE |
| author_facet | Ferreira Carlos G Hoogeland Bas SJ Giaccone Giuseppe Checinska Agnieszka Rodriguez Jose A Kruyt Frank AE |
| author_sort | Ferreira Carlos G |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Activation of caspase-9 in response to treatment with cytotoxic drugs is inhibited in NSCLC cells, which may contribute to the clinical resistance to chemotherapy shown in this type of tumor. The aim of the present study was to investigate the mechanism of caspase-9 inhibition, with a focus on a possible role of TUCAN as caspase-9 inhibitor and a determinant of chemosensitivity in NSCLC cells.</p> <p>Methods</p> <p>Caspase-9 processing and activation were investigated by Western blot and by measuring the cleavage of the fluorogenic substrate LEHD-AFC. Proteins interaction assays, and RNA interference in combination with cell viability and apoptosis assays were used to investigate the involvement of TUCAN in inhibition of caspase-9 and chemosensitivity NSCLC.</p> <p>Results</p> <p>Analysis of the components of the caspase-9 activation pathway in a panel of NSCLC and SCLC cells revealed no intrinsic defects. In fact, exogenously added cytochrome c and dATP triggered procaspase-9 cleavage and activation in lung cancer cell lysates, suggesting the presence of an inhibitor. The reported inhibitor of caspase-9, TUCAN, was exclusively expressed in NSCLC cells. However, interactions between TUCAN and procaspase-9 could not be demonstrated by any of the assays used. Furthermore, RNA interference-mediated down-regulation of TUCAN did not restore cisplatin-induced caspase-9 activation or affect cisplatin sensitivity in NSCLC cells.</p> <p>Conclusion</p> <p>These results indicate that procaspase-9 is functional and can undergo activation and full processing in lung cancer cell extracts in the presence of additional cytochrome c/dATP. However, the inhibitory protein TUCAN does not play a role in inhibition of procaspase-9 and in determining the sensitivity to cisplatin in NSCLC.</p> |
| first_indexed | 2024-04-13T05:17:34Z |
| format | Article |
| id | doaj.art-9a3ced000ae44a7abd1adc37f3372833 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T05:17:34Z |
| publishDate | 2006-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-9a3ced000ae44a7abd1adc37f33728332022-12-22T03:00:50ZengBMCBMC Cancer1471-24072006-06-016116610.1186/1471-2407-6-166TUCAN/CARDINAL/CARD8 and apoptosis resistance in non-small cell lung cancer cellsFerreira Carlos GHoogeland Bas SJGiaccone GiuseppeChecinska AgnieszkaRodriguez Jose AKruyt Frank AE<p>Abstract</p> <p>Background</p> <p>Activation of caspase-9 in response to treatment with cytotoxic drugs is inhibited in NSCLC cells, which may contribute to the clinical resistance to chemotherapy shown in this type of tumor. The aim of the present study was to investigate the mechanism of caspase-9 inhibition, with a focus on a possible role of TUCAN as caspase-9 inhibitor and a determinant of chemosensitivity in NSCLC cells.</p> <p>Methods</p> <p>Caspase-9 processing and activation were investigated by Western blot and by measuring the cleavage of the fluorogenic substrate LEHD-AFC. Proteins interaction assays, and RNA interference in combination with cell viability and apoptosis assays were used to investigate the involvement of TUCAN in inhibition of caspase-9 and chemosensitivity NSCLC.</p> <p>Results</p> <p>Analysis of the components of the caspase-9 activation pathway in a panel of NSCLC and SCLC cells revealed no intrinsic defects. In fact, exogenously added cytochrome c and dATP triggered procaspase-9 cleavage and activation in lung cancer cell lysates, suggesting the presence of an inhibitor. The reported inhibitor of caspase-9, TUCAN, was exclusively expressed in NSCLC cells. However, interactions between TUCAN and procaspase-9 could not be demonstrated by any of the assays used. Furthermore, RNA interference-mediated down-regulation of TUCAN did not restore cisplatin-induced caspase-9 activation or affect cisplatin sensitivity in NSCLC cells.</p> <p>Conclusion</p> <p>These results indicate that procaspase-9 is functional and can undergo activation and full processing in lung cancer cell extracts in the presence of additional cytochrome c/dATP. However, the inhibitory protein TUCAN does not play a role in inhibition of procaspase-9 and in determining the sensitivity to cisplatin in NSCLC.</p>http://www.biomedcentral.com/1471-2407/6/166 |
| spellingShingle | Ferreira Carlos G Hoogeland Bas SJ Giaccone Giuseppe Checinska Agnieszka Rodriguez Jose A Kruyt Frank AE TUCAN/CARDINAL/CARD8 and apoptosis resistance in non-small cell lung cancer cells BMC Cancer |
| title | TUCAN/CARDINAL/CARD8 and apoptosis resistance in non-small cell lung cancer cells |
| title_full | TUCAN/CARDINAL/CARD8 and apoptosis resistance in non-small cell lung cancer cells |
| title_fullStr | TUCAN/CARDINAL/CARD8 and apoptosis resistance in non-small cell lung cancer cells |
| title_full_unstemmed | TUCAN/CARDINAL/CARD8 and apoptosis resistance in non-small cell lung cancer cells |
| title_short | TUCAN/CARDINAL/CARD8 and apoptosis resistance in non-small cell lung cancer cells |
| title_sort | tucan cardinal card8 and apoptosis resistance in non small cell lung cancer cells |
| url | http://www.biomedcentral.com/1471-2407/6/166 |
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