Rasfonin promotes autophagy and apoptosis via upregulation of reactive oxygen species (ROS)/JNK pathway.

Mycology

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

Published: April 2016

Rasfonin is a fungal secondary metabolite demonstrating with antitumour effects. Reactive oxygen species (ROS) are formed as a natural by-product of the normal metabolism of oxygen and have important roles in cell signalling and homeostasis. Studies reported that many fungal secondary metabolites activated either autophagy or apoptosis through ROS generation. In former study, we revealed that rasfonin induced both autophagy and apoptosis, however, whether it promoted aforementioned processes via upregulation of ROS generation remains explored. In the current work, we demonstrated that rasfonin induced autophagy and apoptosis concomitant with a dramatically ROS production. N-Acetylcysteine (NAC), an often used ROS inhibitor, decreased both autophagic flux and caspase-dependent apoptosis by rasfonin. Flow cytometry analysis revealed NAC was able to reduce rasfonin-dependent apoptosis and necrosis. In methanethiosulfonate (MTS) assay, we observed that NAC significantly blocked rasfonin-induced cell viability loss. In addition, we found that rasfonin increased the phosphorylation of c-Jun NH2-terminal kinase (JNK), which was inhibited by NAC. SP600125, an inhibitor of JNK, reduced rasfonin-dependent autophagic flux and apoptosis. Moreover, we demonstrated that rasfonin inhibited the phosphorylation of both 4E-binding protein 1 (4E-BP1) and S6 kinase 1 (S6K1), two main substrates of mammalian target of rapamycin (mTOR). Collectively, rasfonin activated autophagy and apoptosis through upregulation of ROS/JNK signalling.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059153PMC
http://dx.doi.org/10.1080/21501203.2016.1170073DOI Listing

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