Novel 1,4-naphthoquinone derivatives induce apoptosis via ROS-mediated p38/MAPK, Akt and STAT3 signaling in human hepatoma Hep3B cells.
Int J Biochem Cell Biol
; 96: 9-19, 2018 03.
Article
en En
| MEDLINE
| ID: mdl-29326072
ABSTRACT
1,4-Naphthoquinone and its derivatives have shown some efficacy as therapeutic compounds for cancer and inflammation, though their clinical application is limited by their side-effects. To reduce the toxicity of these compounds and optimize their effects, we synthesized two 1,4-naphthoquinone derivatives-2-butylsulfinyl- 1,4-naphthoquinone (BSNQ) and 2-octylsulfinyl-1,4-naphthoquinone (OSNQ)-and investigated their effects and underlying mechanisms in hepatocellular carcinoma cells. BSNQ and OSNQ decreased cell viability and significantly induced apoptosis, accompanied by the accumulation of reactive oxygen species (ROS). However, pretreatment with N-acetyl-l-cysteine, a specific ROS scavenger, blocked apoptosis. Western blot results indicated that BSNQ and OSNQ up-regulated the phosphorylation of p38 and JNK, and down-regulated the phosphorylation of ERK, Akt and STAT3, and that these effects were blocked by N-acetyl-l-cysteine. Furthermore, BSNQ and OSNQ suppressed tumor growth and modulated MAPK and STAT3 signaling in mouse xenografts without detectable effects on body weight or hematological parameters. These results indicate that BSNQ and OSNQ induce apoptosis in human hepatoma Hep3B cells via ROS-mediated p38/MAPK, Akt and STAT3 signaling pathways, suggesting that these 1,4-naphthoquinone derivatives may provide promising new anticancer agents to treat HCC.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Naftoquinonas
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Especies Reactivas de Oxígeno
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Apoptosis
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Carcinoma Hepatocelular
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Sistema de Señalización de MAP Quinasas
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Proteínas Quinasas p38 Activadas por Mitógenos
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Proteínas Proto-Oncogénicas c-akt
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Factor de Transcripción STAT3
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Neoplasias Hepáticas
Límite:
Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article