The Efficacy of Hellebrigenin Against Nasopharyngeal Carcinoma Cells: The Molecular and Bioinformatic Analysis

Nasopharyngeal carcinoma (NPC) is a unique cancer type originating from the nasopharynx. To investigate novel strategies for improving prognosis and reducing the adverse effects of current treatments, this study examined the efficacy of hellebrigenin. Hellebrigenin demonstrated selective cytotoxicity against NPC-BM and NPC-039 cell lines without harming normal nasopharyngeal cells. Treatment with hellebrigenin resulted in G2/M cell cycle arrest in both NPC cell lines. The apoptotic phenomena induced by hellebrigenin included chromatin condensation, increased apoptotic cells and altered mitochondrial membrane potential. Proteomics analysis and the bioinformatic data identified coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) as a candidate oncogene in NPC. Moreover, the combination of CHCHD2 siRNA, CHCHD2 plasmid and hellebrigenin pointed out that CHCHD2 could be a critical mediator of hellebrigenin-induced apoptosis. The combined treatment of hellebrigenin with mitogen-activated protein kinase inhibitors revealed the involvement of the extracellular signal-regulated kinases and c-Jun N-terminal kinases pathways in hellebrigenin-induced apoptosis in NPC cells. In vivo studies demonstrated that hellebrigenin suppressed the tumour volume without affecting body weight, accompanied by the downregulation of Ki67 and CHCHD2 expression. In conclusion, this study provides evidence that hellebrigenin induces NPC apoptosis through regulating CHCHD2 both in vitro and in vivo.