Anti-tumor Effect and Mechanism of Imperatorin Enhances the Cytotoxicity of Cisplatin Osteosarcoma Cells

OBJECTIVE To study the effect of the addition of imperatorin in cisplatin therapy in osteosarcoma(HOS cells) in vitro. METHODS HOS cells were treated with imperatorin and cisplatin, and then their viability was determined by MTT assay in vitro, the expression of Bcl-2 protein family (Mcl-1, Bcl-2, Bcl-xl, Bad and Bax) was evaluating by western blot, and flow cytometry was used for apoptosis detection and measurement of mitochondrial membrane potential. Construct Mcl-1 expression vector, and then detected the role of Mcl-1 vector toward imperatorin plus cisplatin–inducing cytotoxicity in HOS cells by MTT assay. RESULTS Addition of imperatorin significantly enhanced the cytotoxicity of cisplatin to HOS cells in vitro. Mcl-1 expression was down-regulated by imperatorin but not influenced by cisplatin in HOS cells. A combination of imperatorin and cisplatin induced apoptosis and mitochondrial membrane potential collapse more significantly compared with treatment of imperatorin or cisplatin alone. Furthermore, the imperatorin-induced sensitization for cisplatin-cytotoxicity to HOS cells was abolished by the transfection of Mcl-1 expression plasmid. CONCLUSION Combination with imperatorin can enhance the anti-tumor activity of cisplatin to osteosarcoma cells via targeting Mcl-1.