Activation of SAPK/JNK mediated the inhibition and reciprocal interaction of DNA methyltransferase 1 and EZH2 by ursolic acid in human lung cancer cells

摘要: Ursolic acid (UA), a pentacyclic triterpenoid, is known to have anti-tumor activity in various cancers including human non small cell lung cancer (NSCLC). However, the molecular mechanisms underlying action of UA remain largely unknown. Cell viability was measured by MTT assays. Apoptosis analyzed with Annexin V-FITC/PI Detection Kit Flow cytometry. Western blot analysis performed measure phosphorylation and protein expression stress-activated kinase/c-Jun N-terminal kinase (SAPK/JNK), DNMT1 [DNA (cytosine-5)-methyltransferase 1], enhancer zeste 2 polycomb repressive complex subunit (EZH2) SP1. Exogenous SP1 carried out transient transfection We showed that inhibited growth induced apoptosis NSCLC cells dose- time-dependent fashion. Furthermore, we found SAPK/JNK suppressed EZH2. The inhibitor (SP600125) blocked UA-reduced In addition, protein. Conversely, overexpression reversed effect on EZH2 expression, feedback attenuated UA-induced SAPK/JNK. Moreover, exogenous antagonized signaling, growth. Our results show inhibits through SAPK/JNK-mediated inhibition SP1; this turn Overexpression diminishes expression. negative regulation signaling DNMT1, reciprocal interaction contribute overall effects UA. This study leads important new insights into which controls cells.