Dehydrocrenatidine extracted from Picrasmaquassioides induces the apoptosis of nasopharyngeal carcinoma cells through the JNK and ERK signaling pathways.

Abstract

Nasopharyngeal carcinoma (NPC) is an indicator disease in Asia due to its unique geographical and ethnic distribution. Dehydrocrenatidine (DC) is a β-carboline alkaloid abundantly present in Picrasma quassioides (D. Don) Benn, a deciduous shrub or small tree native to temperate regions of southern Asia, and β-carboline alkaloids play anti-inflammatory and antiproliferative roles in various cancers. However, the mechanism and function of DC in human NPC cells remain only partially explored. The present study aimed to examine the cytotoxicity and biochemical role of DC in human NPC cells. The MTT method, cell cycle analysis, DAPI determination, Annexin V/PI double staining, and mitochondrial membrane potential examination were performed to evaluate the effects of DC treatment on human NPC cell lines. In addition, western blotting analysis was used to explore the effect of DC on apoptosis and signaling pathways in related proteins. The analysis results confirmed that DC significantly reduced the viability of NPC cell lines in a dose- and time-dependent manner and induced apoptosis through internal and external apoptotic pathways (including cell cycle arrest, altered mitochondrial membrane potential, and activated death receptors). Western blot analysis illustrated that DC's effect on related proteins in the mitogen-activated protein kinase pathway can induce apoptosis by enhancing ERK phosphorylation and inhibiting Janus kinase (JNK) phosphorylation. Notably, DC induced apoptosis by affecting the phosphorylation of JNK and ERK, and DC and inhibitors (SP600125 and U0126) in combination restored the overexpression of p-JNK and p-ERK. To date, this is the first study to confirm the apoptosis pathway induced by DC phosphorylation of p-JNK and p-REK in human NPC. On the basis of evidence obtained from this study, DC targeting the inhibition of NPC cell lines may be a promising future strategy for NPC treatment.