Brassinin Enhances Apoptosis in Hepatic Carcinoma by Inducing Reactive Oxygen Species Production and Suppressing the JAK2/STAT3 Pathway

Abstract

Plants from the family Brassicaceae produce brassinin (BSN), which is an essential indole phytoalexin. BSN can kill certain types of cancer cells. Using hepatocarcinoma (HCC) cells, we examined the molecular mechanisms of BSN. We found that HCC cell growth was suppressed and apoptosis was induced by BSN via the downregulation of the JAK/STAT3 pathway. The cytoplasmic latent transcription factor STAT3, belonging to the STAT family, acted as both a signal transducer and an activator and was linked to tumor progression and decreased survival. BSN incubation caused HCC cells to produce reactive oxygen species (ROS). By activating caspase-9/-3 and PARP cleavage, Bcl-2 was reduced, and apoptosis was increased. BSN inhibited constitutive STAT3, JAK2, and Src phosphorylation. The JAK/STAT signaling cascade was confirmed by siRNA silencing STAT3 in HCC cells. BSN also suppressed apoptosis by Z-Val-Ala-Asp-Fluoromethylketone (Z-VAD-FMK), an apoptotic inhibitor. N-acetylcysteine (NAC) inhibited the production of ROS and diminished BSN-induced apoptosis. Our findings suggested that BSN has potential as a treatment for cancer.

Keywords

• hepatocellular carcinoma
• brassinin
• STAT3
• transcription factors
• apoptosis
• ROS