The international journal of biochemistry & cell biology, 2018-03, Vol.96, p.9-19
2018
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- Autor(en) / Beteiligte
- Titel
- Novel 1,4-naphthoquinone derivatives induce apoptosis via ROS-mediated p38/MAPK, Akt and STAT3 signaling in human hepatoma Hep3B cells
- Ist Teil von
- The international journal of biochemistry & cell biology, 2018-03, Vol.96, p.9-19
- Ort / Verlag
- Netherlands: Elsevier Ltd
- Erscheinungsjahr
- 2018
- Quelle
- Access via ScienceDirect (Elsevier)
- Beschreibungen/Notizen
- •To improve its antitumor ability, we synthesized two 1,4-naphthoquinone derivatives.•The derivatives showed potent activity in suppressing human hepatoma cell viability.•They also induced apoptosis by a ROS and MAPK/Akt/STAT-dependent mechanism.•In a mouse xenograft model, they suppressed tumor growth without obvious toxicity.•Based on our findings, these derivatives may be promising new chemotherapeutic agents. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1357-2725eISSN: 1878-5875DOI: 10.1016/j.biocel.2018.01.004Titel-ID: cdi_crossref_primary_10_1016_j_biocel_2018_01_004
- Format
- –
- Schlagworte
- 1,4-Naphthoquinone derivatives, Apoptosis, Apoptosis - drug effects, Carcinoma, Hepatocellular - drug therapy, Carcinoma, Hepatocellular - metabolism, Carcinoma, Hepatocellular - pathology, Cell Line, Tumor, Human hepatoma cells, Humans, Liver Neoplasms - drug therapy, Liver Neoplasms - metabolism, Liver Neoplasms - pathology, MAP Kinase Signaling System - drug effects, Naphthoquinones - chemistry, Naphthoquinones - pharmacology, p38 Mitogen-Activated Protein Kinases - metabolism, Proto-Oncogene Proteins c-akt - metabolism, Reactive Oxygen Species - metabolism, ROS, Signaling pathways, STAT3 Transcription Factor - metabolism