Antitumor effect of imperatorin enhances cytotoxicity of doxorubicin to HeLa cells

AIM: To determine whether imperatorin would enhance the effect of doxorubicin therapy on cervical cancer in vitro.METHODS: The viability of HeLa cells treated with imperatorin and doxorubicin was determined by MTT assay in vitro. The expression of Bcl-2 protein family(Mcl-1, Bcl-2, Bcl-xL, Bad and Bax) in HeLa cells treated with imperatorin and doxorubicin was evaluated by Western blot analysis. The apoptosis and mitochondrial membrane potential(ΔΨ_m) in the HeLa cells treated with imperatorin and doxorubicin were analyzed by flow cytometry. A Mcl-1 expression vector was constructed, and its role in the cytotoxicity of imperatorin plus doxorubicin to HeLa cells was detected by MTT assay.RESULTS: Addition of imperatorin significantly enhanced the cytotoxicity of doxorubicin to HeLa cells in vitro. Mcl-1 expression was down-regulated by imperatorin but was not influenced by doxorubicin in the HeLa cells. A combination of imperatorin and doxorubicin induced apoptosis and ΔΨ_m collapse more significantly compared with the treatment with imperatorin or doxorubicin alone. Furthermore, the imperatorin-induced sensitization for doxorubicin cytotoxicity to HeLa cells was abolished by the transfection with Mcl-1 expression plasmid.CONCLUSION: The combination of doxorubicin with imperatorin enhances the antitumor effect of doxorubicin on cervical cancer cells via targeting Mcl-1.