Caged-xanthone from Cratoxylum formosum ssp. pruniflorum inhibits malignant cancer phenotypes in multidrug-resistant human A549 lung cancer cells through down-regulation of NF-kappa B

摘要

Our recent study reported that multidrug-resistant (MDR) human A549 lung cancer cells (A549RT-eto) with the elevated expression of NF-kappa B showed epithelial-mesenchymal transition (EMT), increasing spheroid formation and elevating the expression levels of stemness-related factors, including Oct4, Nanog, Sox2, Bmi1, and Klf4. Therefore, when new therapeutic agents targeting these malignant cancer cells were explored, we found that caged-xanthone (CX) isolated from the roots of Cratoxylum formosum ssp. pruniflorum diminished the expression of NF-kappa B, P-glycoprotein (P-gp) protein levels, cell migration and invasion, and sphere-forming ability of A549RT-eto cells. To address the role of NF-kappa B in these malignant cancer features, we treated A549RT-eto cells with NF-kappa B siRNAs in the present work. We found that the knockdown of NF-kappa B inhibited EMT and sphere formation. Furthermore, co-treatment with CX and NF-kappa B siRNA accelerated the death of apoptotic cells through the decrease of P-gp protein levels. These results suggest that NF-kappa B was involved in malignant cancer phenotypes and MDR in A549RT-eto cells. Taken together, our findings suggest that CX can be a potential therapeutic agent for the treatment of malignant tumor cells.