ML-7 amplifies the quinocetone-induced cell death through akt and MAPK-mediated apoptosis on HepG2 cell line.
Toxicol Mech Methods
; 26(1): 11-21, 2016.
Article
en En
| MEDLINE
| ID: mdl-26446980
ABSTRACT
The study aims at evaluating the combination of the quinocetone and the ML-7 in preclinical hepatocellular carcinoma models. To this end, the effect of quinocetone and ML-7 on apoptosis induction and signaling pathways was analyzed on HepG2 cell lines. Here, we report that ML-7, in a nontoxic concentration, sensitized the HepG2 cells to quinocetone-induced cytotoxicity. Also, ML-7 profoundly enhances quinocetone-induced apoptosis in HepG2 cell line. Mechanistic investigations revealed that ML-7 and quinocetone act in concert to trigger the cleavage of caspase-8 as well as Bax/Bcl-2 ratio up-regulation and subsequent cleavage of Bid, capsases-9 and -3. Importantly, ML-7 weakened the quinocetone-induced Akt pathway activation, but strengthened the phosphorylation of p-38, ERK and JNK. Further treatment of Akt activator and p-38 inhibitor almost completely abolished the ML-7/quinocetone-induced apoptosis. In contrast, the ERK and JNK inhibitor aggravated the ML-7/quinocetone-induced apoptosis, indicating that the synergism critically depended on p-38 phosphorylation and HepG2 cells provoke Akt, ERK and JNK signaling pathways to against apoptosis. In conclusion, the rational combination of quinocetone and ML-7 presents a promising approach to trigger apoptosis in hepatocellular carcinoma, which warrants further investigation.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Quinoxalinas
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Azepinas
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Supervivencia Celular
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Apoptosis
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Quinasas de Proteína Quinasa Activadas por Mitógenos
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Proteínas Proto-Oncogénicas c-akt
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Naftalenos
Límite:
Humans
Idioma:
En
Revista:
Toxicol Mech Methods
Asunto de la revista:
TOXICOLOGIA
Año:
2016
Tipo del documento:
Article