Objective. To investigate the effect of isoimperatorin on nasopharyngeal carcinoma CNE2 cell apoptosis and the role of the MAPK/ERK1/2 signaling pathway in inducing apoptosis. Methods. Real-time cellular analysis technology (RTCA) and MTT were used to detect cell proliferation; Annexin V-FITC/PI dual-fluorescence flow cytometry analysis, Hoechst 33342 staining, and mitochondrial membrane potential detection kit were used to detect cell apoptosis; western blot was used to detect protein expression. Results. Different concentrations of isoimperatorin (10 μM, 20 μM, 30 μM, and 40 μM) significantly inhibited the nasopharyngeal carcinoma CNE2 cell proliferation, and 48 h later, the inhibitory effect of the 40 μM treatment was significantly higher than that of 10 μM and 20 μM. Treatment for 48 h significantly induced nasopharyngeal carcinoma cell apoptosis and resulted in nuclear pyknosis and fragmentation. At the same timepoint, the expression levels of proliferation-related protein PCNA as well as antiapoptosis proteins XIAP, survivin, and Bcl-2 were decreased by drug treatment, the expression level of proapoptosis protein Bax was increased, and the expression of the key MAPK/ERK1/2 signaling pathway proteins p-c-Raf, p-MEK, and p-ERK1/2 of were decreased. After activation of the MAPK/ERK1/2 signaling pathway by isoprenaline hydrochloride (ISO), the efficacy of isoimperatorin to downregulate p-c-Raf, p-MEK, and p-ERK1/2 expressions in the MAPK/ERK1/2 signaling pathway and proliferation-related protein PCNA as well as antiapoptosis proteins XIAP, surviving, and Bcl-2 was reduced compared with that of isoimperatorin alone, the effect of upregulating the proapoptotic protein Bax was reduced, and the apoptosis rate was also decreased. Conclusion. Isoimperatorin can induce nasopharyngeal carcinoma CNE2 cell apoptosis through the MAPK/ERK1/2 signaling pathway.

Introduction. To reveal the mechanisms by which luteolin, the major bioactive component of the Traditional Chinese Medicine (TCM) Polygonum cuspidatum, inhibits proliferation and promotes apoptosis in nasopharyngeal carcinoma (NPC) CNE2 cells. Methods. Based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), bioactive compounds of P. cuspidatum, potential target genes and NPC disease targets of TCMSP were screened, relationship networks were constructed using these potential targets of NPC, and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. The predicted compounds, targets and pathways were corroborated using in vitro experiments, such as MTT, Cytation™ 5 real-time cell monitoring, cell cycle detection, Annexin V-FITC/PI double staining, Hoechst 33342 staining, and mitochondrial membrane potential ( Δ Ψ m ) detection. Results. The results showed that 10 bioactive compounds (OB ≥30% and DL ≥0.18), 157 potential target genes from P. cuspidatum, and 56 common targets related to NPC were found. These included important bioactive compounds such as luteolin, quercetin, and beta-sitosterol. Key common targets included EGFR, MYC, AKT1, CASP3, CCND1, ERBB2, and common targets were enriched for the PI3K-AKT, JAK/STAT, MAPK, and C-type lectin receptor signaling pathways. The binding energy of luteolin for six common targets was less than -5.0 kcal·mol-1. After luteolin (20 μM, and 40 μM) treatment to CNE2 cells for 36 h, cell survival rates decreased, accompanied by cell morphology changes, inhibition of the cell cycle at G2/M phase, and an induction of apoptosis. The expression of the cell proliferation related protein PCNA, the antiapoptosis protein XIAP, and the PI3K-AKT pathway diagram related proteins p-ERK1/2, ERK1/2, AKT, and PI3K, all decreased. Conclusion. Luteolin derived from P. cuspidatum inhibited the proliferation of NPC CNE2 cells and promoted cell apoptosis through the PI3K-AKT signal pathway.