Imperatorin enhances anti-tumor effect of TRAIL on breast cancer by upregulating expression of DR5 on cell surface

AIM: To investigate the synergistic effect of imperatorin on enhancing the anti-tumor effect of TNF-related apoptosis-inducing ligand (TRAIL) on breast cancer and the mechanisms. METHODS: T-47D and MCF-7 breast cancer cells were divided into control group, imperatorin group, TRAIL group, imperatorin+TRAIL group and imperatorin+TRAIL+death receptor 5 (DR5) siRNA group. The viability of T-47D and MCF-7 cells was measured by MTT assay. The apoptosis and mitochondrial membrane potential in T-47D cells were analyzed by flow cytometry. Western blot and flow cytometry analysis were performed to evaluate the expression of DR5 on T-47D cell surface and the activation of caspase-8 and caspase-3. RESULTS: Imperatorin significantly enhanced the inhibition of cell viability induced by TRAIL of T-47D and MCF-7 cells, and significantly increased the apoptosis of T-47D cells induced by TRAIL. Imperatorin treatment ob-viously induced upregulation of DR5 expression and production of reactive oxygen species in the T-47D cells. In addition, imperatorin enhanced the TRAIL-induced damage of mitochondrial membrane potential and activation of caspase-8 and caspase-3. CONCLUSION: Imperatorin enhances the anti-tumor effect of TRAIL on breast cancer via upregulating the expression of DR5.