Effects of Combined Crocin and Epirubicin on Apoptosis and Cell Cycle Pathways in a Human Cervical Cancer Cell Line

Background: Despite using various chemotropic drugs, the therapy strategies of cervical cancer are not satisfactory. Researchers tended to examine anti-proliferative effects of different botanical components such as crocin on several cancers. Objectives: We investigated the anti-cancer mechanisms of crocin and epirubicin combination on cancer cervical cells to use fewer toxic components. Methods: By MTT, Hoechst staining and flowcytometry techniques, cell proliferation inhibitory, and apoptosis induction effects of crocin and epirubisin combination on a cervical cancer cell line (OV2008) were determined. Then, alteration expression of the Bax, Bcl2, and P21 genes were also investigated through real-time polymerase chain reaction (real-time PCR). Results: The MTT results showed that crocin and epirubicin stopped proliferation of OV2008 cells. These substances had a simple additive effect after 72 hours treatment. The Hoechst staining illustrated that apoptosis significantly increased after combination therapy. The results of the cell cycle analysis showed that the percentage of dead cells was increased compared to the control group. Also, the number of cells, introduced in all of cell cycle phases, was changed, too. Moreover, real-Time PCR results showed that epiburicin 3.75 µm/mL and crocin 2000 µm/mL led to Bax and P21 up-regulated and Bcl2 down-regulated. Conclusions: Crocin can be used in companion with fewer dose of chemotropic drugs to get better results in cancer therapy and can be more effective on the reduction of drug resistance due to target the main regulators of apoptosis. Nonetheless, more surveys are needed to enlighten their molecular mechanisms.