Isoginkgetin Induces Caspase Cascade Activation and Cell Apoptosis via JNK Signaling in Oral Cancer.

Isoginkgetin (IGG), a naturally occurring biflavonoid found in the leaves of many medicinal plants, is known to inhibit pre-mRNA splicing and display anti-cancer characteristics. However, knowledge regarding the use of IGG on oral squamous cell carcinoma (OSCC) lags behind that on the other common malignancies. The aim of this study is to explore whether IGG hinders OSCC proliferation and further investigated its oncostatic actions. We demonstrated that exposure of OSCC cell lines (HSC-3 and SCC-9) to IGG significantly diminished cell viability and induced apoptotic cell death. Furthermore, levels of several tentative apoptosis suppressors (cIAP-1 and XIAP) were decreased in IGG-treated HSC-3 and SCC-9 cells, accompanied with increased cleavage of caspases. Of note, such activation of caspase cascades by IGG was reduced by pharmaceutical inhibition of c-Jun N-terminal kinase (JNK) via a specific kinase antagonist, suggesting a functional connection of JNK activity with caspase activation during IGG-induced oral cancer cell apoptosis. In conclusion, we exhibited that IGG hampered cell viability and stimulated apoptotic events in OSCC, driven by a JNK-dependent pathway of caspase activations. Our findings present new insights into applications of a natural biflavonoid compound in fighting oral carcinogenesis.