RT Journal Article
SR Electronic
T1 Combinations of Platinums and Selected Phytochemicals as a Means of Overcoming Resistance in Ovarian Cancer
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 541
OP 545
VO 34
IS 1
A1 FAZLUL HUQ
A1 JUN Q. YU
A1 PHILIP BEALE
A1 CHARLES CHAN
A1 LALIA ARZUMAN
A1 MEHER U. NESSA
A1 MOHAMMED E. H. MAZUMDER
YR 2014
UL http://ar.iiarjournals.org/content/34/1/541.abstract
AB Cancer sufferers are often found to use herbal products along with targeted therapy although not much information (whether beneficial or harmful) is available about the effects of such combinations. In this study, we investigated synergism from the combination of platinum drugs and a number of tumour-active phytochemicals including curcumin, epigallocatechin-3-gallate, thymoquinone, genistein, resveratrol, betulinic acid and ursolic acid in three human ovarian cancer cell lines A2780, A2780cisR and A2780ZD0473R, as a function of concentration and the sequence of administration. Both the dose–effect curves and combination indices show that the binary combinations of platinum drugs with the phytochemicals exert concentration- and sequence-dependent synergism in the cell lines. Generally the degree of synergism is found to be greater in sequenced administration such as 0/2 h, 2/0 h, 0/4 h and 4/0 h than the bolus. The variation in the nature of the combined drug action from being highly synergistic to antagonistic with the change in sequence of administration clearly indicates that the action of one drug modulates that of the other (towards the induction or inhibition of apoptosis). We have also used sequenced combinations of platinum drugs and bortezomib (a proteasome inhibitor that prevents cisplatin-induced proteasomal degration of copper transporter CTR1) to enhance cellular platinum accumulation and the level of platinum–DNA binding especially in the resistant human ovarian tumour models. Proteomic studies to identify the key proteins associated with platinum resistance are ongoing. We have identified 59 proteins associated with platinum resistance in ovarian tumor models.