Hellebrigenin induces oral cancer cell apoptosis by modulating MAPK signalling and XIAP expression

• Published in: Journal of cellular and molecular medicine Vol. 28; no. 2; pp. e18071 - n/a
• Main Authors: Hsieh, Ming‐Ju, Lin, Chia‐Chieh, Lo, Yu‐Sheng, Ho, Hsin‐Yu, Chuang, Yi‐Ching, Chen, Mu‐Kuan
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.01.2024; John Wiley and Sons Inc
• Subjects: Antibodies; Antitumor activity; Apoptosis; Apoptosis - physiology; Bcl-2 protein; Bcl-x protein; Brain cancer; Bufanolides; Cancer therapies; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Caspase-3; Cdc2 protein; Cell cycle; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cell Proliferation; Chemotherapy; Cyclins; Cytotoxicity; Down-regulation; hellebrigenin; Humans; MAP kinase; Medical prognosis; Metastasis; Mouth Neoplasms - drug therapy; Mouth Neoplasms - genetics; Mouth Neoplasms - pathology; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Original; Phosphorylation; Proteins; Public health; Signal Transduction; Software; Squamous cell carcinoma; Therapeutic applications; Tumors; X-Linked Inhibitor of Apoptosis Protein - genetics; X-Linked Inhibitor of Apoptosis Protein - metabolism; XIAP; XIAP protein; United States > US; XIAP; apoptosis; oral squamous cell carcinoma; hellebrigenin
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.18071

Oral squamous cell carcinoma (OSCC), which accounts for 90% of all oral cancers, has become a public health crisis worldwide. despite advances in therapeutic interventions, the prognosis remains poor for advanced‐stage OSCC. In this study, we investigate the anticancer activity and the mode of action of hellebrigenin in human OSCC. The findings demonstrated that hellebrigenin exerted cytotoxic effects in OSCC cells through cell cycle arrest at the G2/M phase and downregulation of cell cycle‐related proteins (cyclins A2, B1 and D3, Cdc2, CDK4 and CDK6). Moreover, hellebrigenin caused activation of PARP and caspase 3, 8 and 9, followed by downregulation of antiapoptotic proteins (Bcl‐2 and Bcl‐xL) and upregulation of pro‐apoptotic proteins (Bax and Bak). The hellebrigenin treatment also increased Fas, DR5, DcR2 and DcR3 expressions in oral cancer cells, indicating the compound causes oral cancer cell apoptosis through both intrinsic and extrinsic pathways. Regarding upstream signalling, hellebrigenin was found to reduce the phosphorylation of ERK, p38, and JNK, indicating that hellebrigenin triggers caspase‐mediated apoptosis by downregulating MAPK signalling pathway. Finally, the human apoptosis array findings revealed that hellebrigenin specifically suppressed the expression of XIAP to execute its pro‐apoptotic activities. Taken together, the study suggests that hellebrigenin can act as a potent anticancer compound in human OSCC.