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| Content Provider | PubMed Central |
|---|---|
| Author | Sung, Myong-hee Lorena, Bagain Chen, Zhong Karpova, Tatiana Yang, Xinping Christopher, Silvin Voss, Ty Mcnally, James Waes, Carter Van Hager, Gordon L. |
| Abstract | NF-κB influences the initiation, progression, and maintenance of diverse cancer types. Despite current therapeutic efforts to block hyperactive NF-κB in cancer cells, the in vivo effects of a drug upon this complex pathway are unclear. We monitored NF-κB activity and a fast-expressing reporter level simultaneously in head and neck squamous carcinoma cells by quantitative live microscopy. The real time single cell assay revealed the TNF-α induced oscillation of NF-κB was echoed by equally dynamic reporter expression rate. Bortezomib is a proteasome inhibitor whose anti-cancer action is partly mediated through inhibition of NF-κB. When administered to pre-activated cells, the drug gave rise to distinct inhibition dynamics, with discrete pulses of reporter induction remaining for hours. These findings suggest that, contrary to a simplistic presumption for a pathway ‘blockade’, the network dynamics and the intracellular pharmacokinetics of the inhibitor must be critically evaluated in developing strategies for optimal intervention of oncogenic pathways. |
| Related Links | http://dx.doi.org/10.1124/mol.108.049114 |
| Starting Page | 1215 |
| File Format | |
| ISSN | 15210111 |
| e-ISSN | 15210111 |
| Journal | Molecular pharmacology |
| Issue Number | 5 |
| Volume Number | 74 |
| Language | English |
| Publisher Date | 2008-11-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Molecular Medicine Pharmacology |
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