1,4-Naphthoquinone Triggers Nematode Lethality by Inducing Oxidative Stress and Activating Insulin/IGF Signaling Pathway in Caenorhabditis elegans

Plant-parasitic nematodes are destructive pathogens causing enormous economic losses worldwide. With the withdrawal of fumigants, organophosphates and carbamates, pathogenic nematode control is more difficult. Phytochemicals are the plant secondary metabolites and are friendly for men and the environment. For developing new nematocidal candidates, we screened 790 phytochemicals using the model organism Caenorhabditis elegans and found 10 active compounds, 3 of which were further evaluated for their inhibitory activities against egg hatching of C. elegans and J2 Meloidogyne incognita. Among them, 1,4-naphthoquinone (1,4-NQ) was the only compound that could kill more than 50% of targets at 50 μg/mL, prompting us to investigate how 1,4-NQ triggers nematode lethality. In C. elegans, we observed that 1,4-NQ could influence reactive oxygen production, superoxide dismutase activity, and the heat-shock transcription factor (HSF)-1 pathway, which indicated that 1,4-NQ stimulated significant oxidative stress. Furthermore, using quantitative RT-PCR and transgenetic nematodes, we revealed that 1,4-NQ lethality was related to the Insulin/IGF signaling (IIS) pathway, and the effect of 1,4-NQ on IIS pathway related genes indicated that 1,4-NQ could activate this pathway and suppress the expression of DAF-16 target genes. The triggering of oxidative stress and activation of the IIS pathway indicated that 1,4-NQ operates through the generation of oxygen radicals, which can be lethal to C. elegans, thus making it an interesting lead compound for the development of future nematocides.