The Determination of Cisplatin and Luteolin Synergistic Effect on Colorectal Cancer Cell Apoptosis and Mitochondrial Dysfunction by Fluorescence Labelling

Abstract

Despite the initial success of chemotherapy in the treatment of colorectal carcinoma (CRC), the recurrence of the disease shows that the tumor response is limited by the formation of drug resistance and cannot be kept under control. These drawbacks are associated with the cytostatic chemotherapeutic agent cisplatin (Cis). Combination treatment with different anticancer drugs could increase the therapeutic efficacy of combined therapies by allowing the use of lower, less toxic doses to achieve more efficient destruction of cancer cells. Luteolin (LU) has been studied with other anticancer drugs due to its anticancer cell inhibitory properties and has been shown to sensitize the cytotoxicity induced by various anticancer drugs in several cancer cells. Therefore, in this work, the CompuSyn system was used to investigate different Cis + LU combinations in HCT116 colorectal cancer cells. Immunofluorescence was used to measure mitochondrial membrane potential (MMP) and cell death. As a result, a synergistic effect was observed in 5 of the 7 doses tested. Apoptosis/necrosis resulting from chemotherapy resistance was confirmed by Hoechst/ PI -double staining and mitochondrial dysfunction were determined by Rodamine123 (Rho123). Luteolin could thus be used in medicine to provide more effective cancer therapy in appropriate doses, which promises a promising future in clinical application.