Abstract
NF-E2-related factor 2 (NRF2) regulates transcription of phase II cytoprotective enzymes to protect normal cells against oxidative stress. However, a high level of NRF2 offers a growth advantage, chemoresistance, and radioresistance in cancer. In the present study, we have identified convallatoxin as a novel inhibitor of NRF2/ARE. Suppression of NRF2 by convallatoxin was not transcriptionally mediated, but regulated at the level of proteolysis. Convallatoxin activated GSK-3β and suppression of NRF2 by convallatoxin required the Neh6 domain. Convallatoxin sensitised A549 cells to 5-fluorouracil-mediated cell death by promoting apoptosis. Together, our results provide evidence that convallatoxin might be useful as a chemotherapeutic adjuvant due to its ability to suppress NRF2/ARE.
| Original language | English |
|---|---|
| Pages (from-to) | 1416-1423 |
| Number of pages | 8 |
| Journal | Free Radical Research |
| Volume | 52 |
| Issue number | 11-12 |
| DOIs | |
| State | Published - 2 Dec 2018 |
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
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SDG 3 Good Health and Well-being
Keywords
- 5-Fluorouracil (5-FU)
- antioxidant response element (ARE)
- convallatoxin
- NRF2
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