Combined treatment of menadione and calcitriol increases the antiproliferative effect by promoting oxidative/nitrosative stress, mitochondrial dysfunction, and autophagy in breast cancer MCF-7 cells.
Can J Physiol Pharmacol
; 98(8): 548-556, 2020 Aug.
Article
en En
| MEDLINE
| ID: mdl-32762631
The aim of this study was to determine new insights into the molecular mechanisms involved in the antiproliferative action of menadione + calcitriol (MEN+D) on MCF-7 cells. After 24 h, MEN+D inhibited the cell growth but was not observed with each single treatment. The combined drugs reduced the mitochondrial respiration at that time, as judged by an increase in the proton leak and a decrease in the ATP generation and coupling efficiency. At longer times, 48 or 96 h, either D or MEN reduced the proliferation, but the effect was higher when both drugs were used together. The combined treatment increased the superoxide anion ([Formula: see text]) and nitric oxide (NOâ¢) contents as well as acidic vesicular organelles (AVOs) formation. The percentage of cells showing the lower mitochondrial membrane potential (ΔΨm) was highly increased by the combined therapy. LC3-II protein expression was enhanced by any treatment. In conclusion, the antiproliferative action of MEN+D involves oxidative/nitrosative stress, mitochondrial alteration, and autophagy. This combined therapy could be useful to treat breast cancer cells because it inhibits multiple oncogenic pathways more effectively than each single agent.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
/
Neoplasias de la Mama
/
Calcitriol
/
Estrés Oxidativo
/
Vitamina K 3
/
Estrés Nitrosativo
/
Mitocondrias
Límite:
Humans
Idioma:
En
Revista:
Can J Physiol Pharmacol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Argentina
Pais de publicación:
Canadá