Combination between platinum drugs and selected phytochemicals in colorectal cancer
Drug resistance which may be intrinsic or acquired remains a major problem in cancer therapy including colorectal cancer. Synergistic combinations of tumour active phytochemicals and targeted therapy may provide an affordable means of overcoming drug resistance in cancer.
This study aims to apply sequenced combinations of tumour active platinum drugs used in the clinic with selected phytochemicals including resveratrol, thymoquinone, capsaicin and quercetin to colorectal tumour models
The MTT reduction assay was used to determine the activity of the compounds against colorectal cancer cell lines HT29/219, Caco-2, LIM1215 and LIM2405. Both sequence- and concentration-dependent synergism in activity resulting from the combinations of platinum with the selected phytochemicals was investigated with drugs added at constant ratios of their IC50 values where combination indices ere used as a measure of combined drug action.
The IC50 values (µM) of cisplatin, resveratrol and thymoquinone against HT29 were 6.92, 47.46 and 12.03 respectively while the values against Caco-2 were 26.02, 40.57 and 6.63 respectively. Combinations of cisplatin and phytochemicals administered to HT29 and Caco-2 cell lines are slightly antagonistic at ED50 and mildly synergistic to additive at ED90. The IC50 values (µM) of oxaliplatin, capsaicin and quercetin against LIM1215 were 1.25, 91.90 and 65.80 while the values against LIM2405 were 0.7, 50.26 and 28.46 respectively. All combinations of oxaliplatin with quercetin and capsaicin have produced synergistic outcomes in LIM2405 cell line and more so at high concentrations.
The results provide support to the idea that combinations of tmour active phytochemicals and targeted therapy can provide a means of overcoming drug resistance in colorectal cancer.