Luteolin impairs hypoxia adaptation and progression in human breast and colon cancer cells.
Eur J Pharmacol
; 881: 173210, 2020 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-32526242
Hypoxia-inducible factors (HIFs) are the force which drives hypoxic cancer cells to a more aggressive and resistant phenotype in a number of solid tumors, including colorectal and breast cancer. Results from recent studies suggest a role for HIF-1 in immune evasion and cancer stem cell phenotype promotion, establishing HIF-1 as a potential therapeutic target. Thus, identifying new compounds that might inhibit HIF1 activity, or at least exert antiproliferative effects that are unaffected by HIF1-dependent adaptations, is an attractive goal for the management of hypoxic tumors. Here we show that the flavonoid luteolin exerts a significant cytotoxic effect on the colon cancer cell line HCT116 and the breast adenocarcinoma cell line MDA-MB231, by inducing both apoptotic and necrotic cell death, and that this effect is not impaired by HIF-1 activation. In these cells, luteolin also stimulates autophagy; however this seems to be part of a protective response, rather than contribute to the cytotoxic effect. Interestingly, luteolin induces a decrease in HIF-1 transcriptional activity. This is accompanied by a decrease in the levels of protein markers of stemness and invasion, and by a reduction of migratory capacity of the cells. Taken together, our results suggest that luteolin could be developed into a useful therapeutic agent aimed at hypoxic tumors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Neoplasias del Colon
/
Luteolina
/
Subunidad alfa del Factor 1 Inducible por Hipoxia
/
Antineoplásicos Fitogénicos
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Países Bajos