| Added by | celine.gongora |
|---|---|
| Group name | EquipeCG |
| Item Type | Journal Article |
| Title | The Anti-Cancer Drug Dabrafenib Is a Potent Activator of the Human Pregnane X Receptor |
| Creator | Creusot et al. |
| Author | Nicolas Creusot |
| Author | Matthieu Gassiot |
| Author | Elina Alaterre |
| Author | Barbara Chiavarina |
| Author | Marina Grimaldi |
| Author | Abdelhay Boulahtouf |
| Author | Lucia Toporova |
| Author | Sabine Gerbal-Chaloin |
| Author | Martine Daujat-Chavanieu |
| Author | Alice Matheux |
| Author | Roger Rahmani |
| Author | Céline Gongora |
| Author | Alexandre Evrard |
| Author | Philippe Pourquier |
| Author | Patrick Balaguer |
| Abstract | The human pregnane X receptor (hPXR) is activated by a large set of endogenous and exogenous compounds and plays a critical role in the control of detoxifying enzymes and transporters regulating liver and gastrointestinal drug metabolism and clearance. hPXR is also involved in both the development of multidrug resistance and enhanced cancer cells aggressiveness. Moreover, its unintentional activation by pharmaceutical drugs can mediate drug-drug interactions and cause severe adverse events. In that context, the potential of the anticancer BRAF inhibitor dabrafenib suspected to activate hPXR and the human constitutive androstane receptor (hCAR) has not been thoroughly investigated yet. Using different reporter cellular assays, we demonstrate that dabrafenib can activate hPXR as efficiently as its reference agonist SR12813, whereas it does not activate mouse or zebrafish PXR nor hCAR. We also showed that dabrafenib binds to recombinant hPXR, induces the expression of hPXR responsive genes in colon LS174T-hPXR cancer cells and human hepatocytes and finally increases the proliferation in LS174T-hPXR cells. Our study reveals that by using a panel of different cellular techniques it is possible to improve the assessment of hPXR agonist activity for new developed drugs. |
| Publication | Cells |
| Volume | 9 |
| Issue | 7 |
| Pages | E1641 |
| Date | 2020-07-08 |
| Journal Abbr | Cells |
| Language | eng |
| DOI | 10.3390/cells9071641 |
| ISSN | 2073-4409 |
| Library Catalog | PubMed |
| Extra | PMID: 32650447 PMCID: PMC7407672 |
| Tags | Antineoplastic Agents, Cell Line, Tumor, Cell Proliferation, colon and liver cancer cells, corresponding, dabrafenib, HeLa Cells, Hep G2 Cells, hPXR, Humans, Imidazoles, original, Oximes, Pregnane X Receptor, proliferation, Protein Binding |
| Date Added | 2022/08/29 - 15:27:56 |
| Date Modified | 2022/08/29 - 16:23:42 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
