Lasiodin Inhibits Proliferation of Human Nasopharyngeal Carcinoma Cells by Simultaneous Modulation of the Apaf-1/Caspase, AKT/MAPK and COX-2/NF-κB Signaling Pathways

摘要: Rabdosia serra has been widely used for the treatment of various human diseases. However, antiproliferative effects and underlying mechanisms compounds in this herb remain largely unknown. In study, an compound against nasopharyngeal carcinoma (NPC) cells from was purified identified as lasiodin (a diterpenoid). The with inhibited cell viability migration. Lasiodin also mediated morphology change induced apoptosis NPC cells. Apaf-1 expression, triggered cytochrome-C release, stimulated PARP, caspase-3 caspase-9 cleavages, thereby activating apoptotic pathways. significantly phosphorylations AKT, ERK1/2, p38 JNK proteins. pretreatment AKT or MAPK-selective inhibitors considerably blocked lasiodin-mediated inhibition proliferation. Moreover, COX-2 abrogated NF-κB binding to promoter, promoted translocation nuclei cytosol. a COX-2-selective inhibitor lasiodin-induced These results indicated that simultaneously activated Apaf-1/caspase-dependent pathways suppressed AKT/MAPK COX-2/NF-κB signaling This study suggested could be promising natural prevention NPC.