Homoharringtonine stabilizes secondary structure of guanine-rich sequence existing in the 5'-untranslated region of Nrf2.
Bioorg Med Chem Lett
; 29(16): 2189-2196, 2019 08 15.
Article
en En
| MEDLINE
| ID: mdl-31270017
Homoharringtonine, known as omacetaxine mepesuccinate, is a pharmaceutical drug substance approved for treatment of chronic myeloid leukemia. Here, we report that homoharringtonine (HHT) is a novel chemical inhibitor of NRF2. HHT significantly suppressed NRF2 and ARE-dependent gene expression in human lung carcinoma A549 cells. HHT stabilized secondary structure of guanine-rich sequence existing in the 5'-untranslated region (5'-UTR) of Nrf2 and sensitized A549 cells to etoposide-induced apoptosis. To the best of our knowledge, HHT is the first type of transcriptional inhibitor of Nrf2 that stabilizes guanine-rich sequence existing in the 5'-UTR. Our study also provides a novel mechanism of action underlying how HHT exerts anti-carcinogenic effects in cancer cells.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Regiones no Traducidas 5'
/
Factor 2 Relacionado con NF-E2
/
Homoharringtonina
/
Guanina
/
Antineoplásicos Fitogénicos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Corea del Sur