芹菜素藉由腫瘤壞死因子接受器及Bcl-2路徑誘導頭頸部鱗狀細胞癌凋亡並增強5-fluorouracil及cisplatin之敏感性

Abstract

Apigenin, a naturally occurring plant flavone, may have chemopreventive and therapeutic potentials as an anti-inflammatory, antioxidant and apigenin against malignant tumors. However, the anti-tumor effect of apigenin on human head and neck squamous cell carcinoma (HNSCC) is not fully understood. In this study, apigenin inhibits cell growth and induces cell cycle arrest during the G2/M phase in well differentiated HNSCC SCC25 cells and epidermoid carcinoma A431 cells. Apigenin has cancer preventive properties, antioxidant capacity, ability to inhibit lipid peroxidation, and protective murine normal embryonic liver BNLCL2 cells against oxidative damage. Apigenin increased intracellular reactive oxygen species (ROS) levels, depleted intracellular-reduced glutathione (GSH), and induced cell apoptosis via tumor necrosis factor receptor (TNF-R), TNF-related apoptosis-inducing ligand receptor (TRAIL-R), and Bcl-2-mediated caspase-dependent cell death pathways in SCC25 cells but Fas signal is not. The combination of apigenin with 5-fluorouracil (5-Fu) or cisplatin dramatically increased death of SCC25 cells in a dose-dependent manner; this property may be exploited to reverse HNSCC insensitivity to 5-Fu and cisplatin. These analytical findings suggest that apigenin may be a good candidate for additional evaluation as a cancer therapeutic agent against HNSCC cells.