Dose and Sequence Dependent Synergism from the Combination of Oxaliplatin with Emetine and Patulin Against Colorectal Cancer

Background: Colorectal cancer is the third most commonly diagnosed cancer in the world, causing many deaths every year. Combined chemotherapy has opened a new horizon in treating colorectal cancer. The objective of the present study is to investigate the activity of oxaliplatin in combination with emetine and patulin against colorectal cancer models. Methods: IC50 values of oxaliplatin, emetine and patulin were determined against human colorectal cancer cell lines (HT-29 and Caco-2) using MTT reduction assay. Synergistic, antagonistic and additive effects from the selected binary combinations were determined as a factor of sequence of administration and added concentrations. Proteomics was carried out to identify the proteins which were accountable for combined drug action applying to the selected drug combination. Results: Oxaliplatin in combination with patulin produced synergism against human colorectal cancer models depending on dose and sequence of drug administration. Bolus administration of oxaliplatin with patulin proved to be the best in terms of synergistic outcome. Altered expressions of nine proteins (ACTG, PROF1, PPIA, PDIA3, COF1, GSTP1, ALDOA, TBA1C and TBB5) were considered for combined drug actions of oxaliplatin with patulin. Conclusion: Bolus administration of oxaliplatin with patulin has the potential to be used in the treatment of colorectal cancer, and would warrant further evaluation using suitable animal model.