Inhibition of cell growth and sensitization of ovarian cancer cells to platinums by combination with phytochemicals
Meher Un Nessa
Discipline of Biomedical Science
School of Medical Sciences
Sydney Medical School
The University Of Sydney
S 209,Cumberland Campus C42
75 East Street (PO Box 170) Lidcombe
NSW,1825
Australia
Abstract:
Development of chemo-resistance is one of the major limitations of platinum drugs in cancer chemotherapy. One way of overcoming resistance is to use combination of drugs with different modes of action so that they can act synergistically in combination. In this study, combinations of selected phytochemicals (anethole, betulinic acid, capsaicin, curcumin, genestein, paclitaxel, quercetin, resveratrol and thymoquinone) and platinums (cisplatin and oxaliplatin) are used to overcome resistance in ovarian tumour model. Cell viability is quantified by MTT reduction assay and combination results are analyzed using Calcusyn software. It is found that all of the selected phytochemicals can inhibit growth of parent (A2780) and resistant cells (A2780cisR and A2780ZD473R). Although some of the bolus combinations are found to be antagonistic, sequential additions with 2 h gaps are all found to be synergistic with greater synergism being observed when the phytochemicals were administered first. The sequence-dependent synergism is also true for combination of the phytochemicals with oxaliplatin. The results suggest that the selected phytochemicals can inhibit growth and can sensitize cancer cells to platinum action, thus suggesting a possible means of overcoming drug resistance and opening a new window for cancer treatment.
Keywords: Drug resistance, combination, phytochemicals, platinum drugs, synergism
