Effects of Tetrandrine on the Apoptosis of Cisplatin-resistant Oral Cancer Cells

Abstract

Background Cisplatin, the first-line drug for chemotherapy, often has limited treatment efficacy because of resistance and cancer recurrence mechanisms. Tetrandrine is a unique secondary metabolite of Stephania tetrandra. As a traditional Chinese medicine agent, tetrandrine has been reported to have antioxidant, anti-inflammatory, antitumor, and antiangiogenesis activities and has been shown to inhibit the proliferation and angiogenesis of colorectal, lung, and breast cancer cells; potential mechanisms underlying its activities include the promotion of tumor cell apoptosis, promotion of cell cycle arrest, and intensification of reactive oxygen species (ROS) production. Objectives The main treatments for oral cancer are chemotherapy, surgery, and radiotherapy; these treatments are often used in combination. Cancer cells easily develop cisplatin resistance; therefore, we investigated tetrandrine’s potential as a therapy for overcoming resistance to oral cancer drugs. Materials and Methods We used the cisplatin-resistant oral cancer CAR cell line (CAL27) as a research objected and applied inhibitor treatment to clarify the role of tetrandrine in cell death and mitochondrial dysfunction. Results Tetrandrine could effectively inhibit CAR cell proliferation and induce apoptosis, with a corresponding increase in ROS production in mitochondria. Moreover, tetrandrine increased caspase-9 and caspase-3 activity in CAR cells and induced apoptotic mRNA, caspase-3/-9, AIF, and Endo G overexpression. Our results indicate that tetrandrine induces apoptosis in CAR cells through a mitochondrial-dependent signaling pathway.