| Autor: |
Laura Mezzanotte, Na An, Isabel M Mol, Clemens W G M Löwik, Eric L Kaijzel |
| Jazyk: |
angličtina |
| Rok vydání: |
2014 |
| Předmět: |
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| Zdroj: |
PLoS ONE, Vol 9, Iss 1, p e85550 (2014) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0085550 |
| Popis: |
Evaluation of novel drugs for clinical development depends on screening technologies and informative preclinical models. Here we developed a multicolor bioluminescent imaging platform to simultaneously investigate transcription factor NF-κB signaling and apoptosis.The human breast cancer cell line (MDA-MB-231) was genetically modified to express green, red and blue light emitting luciferases to monitor cell number and viability, NF-κB promoter activity and to perform specific cell sorting and detection, respectively. The pro-luciferin substrate Z-DEVD-animoluciferin was employed to determine apoptotic caspase 3/7 activity. We used the cell line for the in vitro evaluation of natural compounds and in vivo optical imaging of tumor necrosis factor TNFα-induced NF-κB activation.Celastrol, resveratrol, sulphoraphane and curcumin inhibited the NF-κB promoter activity significantly and in a dose dependent manner. All compounds except resveratrol induced caspase 3/7 dependent apoptosis. Multicolor bioluminescence in vivo imaging allowed the investigation of tumor growth and NF-κB induction in a mouse model of breast cancer.Our new method provides an imaging platform for the identification, validation, screening and optimization of compounds acting on NF-κB signaling and apoptosis both in vitro and in vivo. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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