Abstract |
1-(3,5-Dimethoxyphenyl)-4-[(6-fluoro-2-methoxyquinoxalin-3-yl)aminocarbonyl] piperazine (RX-5902) exhibits strong growth inhibition in various human cancer cell lines with IC50 values ranging between 10 and 20 nM. In this study, we demonstrate that p68 RNA helicase is a cellular target of RX-5902 by the drug affinity responsive target stability (DARTS) method, and confirmed the direct binding of (3) H-labeled RX-5902 to Y593 phospho-p68 RNA helicase. We further demonstrated RX-5902 inhibited the β- catenin dependent ATPase activity of p68 RNA helicase in an in vitro system. Furthermore, we showed that treatment of cancer cells with RX-5902 resulted in the downregulation of the expression of certain genes, which are known to be regulated by the β- catenin pathway, such as c-Myc, cyclin D1 and p-c-Jun. Therefore, our study indicates that the inhibition of Y593 phospho-p68 helicase - β- catenin interaction by direct binding of RX-5902 to Y593 phospho-p68 RNA helicase may contribute to the anti- cancer activity of this compound.
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Authors | Gina Chun Kost, Mi Young Yang, Liangwei Li, Yinwei Zhang, Chia-Yi Liu, Deog Joong Kim, Chang-Ho Ahn, Young Bok Lee, Zhi-Ren Liu |
Journal | Journal of cellular biochemistry
(J Cell Biochem)
Vol. 116
Issue 8
Pg. 1595-601
(Aug 2015)
ISSN: 1097-4644 [Electronic] United States |
PMID | 25649741
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 Wiley Periodicals, Inc. |
Chemical References |
- Antineoplastic Agents
- Piperazines
- Quinoxalines
- RX-5902
- beta Catenin
- DEAD-box RNA Helicases
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Topics |
- Antineoplastic Agents
(pharmacology)
- Binding Sites
(drug effects)
- Cell Line, Tumor
- DEAD-box RNA Helicases
(chemistry, metabolism)
- Humans
- Neoplasms
(drug therapy, metabolism)
- Phosphorylation
- Piperazines
(pharmacology)
- Protein Binding
(drug effects)
- Quinoxalines
(pharmacology)
- Signal Transduction
(drug effects)
- beta Catenin
(metabolism)
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