NF-kappab facilitates oridonin-induced apoptosis and autophagy in HT1080 cells through a p53-mediated pathway.

In this study, we investigated the molecular mechanisms involving in oridonin-induced apoptosis and autophagy. We found that apoptosis and autophagy were simultaneously induced by oridonin time-dependently in HT1080 cells, and inhibition of autophagy by 3MA decreased oridonin-induced apoptosis, indicating that they act in synergy to mediate cell death. In addition, treatment with oridonin caused an increase in NF-kappaB and p53 activities in a time-dependent manner. Inhibition of NF-kappaB or p53 activation by its specific inhibitor PDTC or pifithrin-alpha respectively, significantly reduced both oridonin-induced apoptosis and autophagy accompanied by the decrease in Beclin 1 and LC3 levels. Further experiments confirmed that oridonin-induced p53 activation was reduced by the NF-kappaB inhibitor whereas the activation of NF-kappaB was not affected by p53 inhibition. Taken together, these results demonstrate that NF-kappaB promotes oridonin-induced apoptotic and autophagic cell death through regulating p53 activation in HT1080 cells.