title: Synergism from the combination of oxaliplatin with selected phytochemicals in human ovarian cancer cell lines.
abstract: Oxaliplatin (Oxa) is a third generation platinum drug currently in clinical use for the treatment against colorectal cancer. Although it has a somewhat different spectrum of activity than cisplatin (Cis), it too has two major limitations, namely problems of side-effects and drug resistance. In this study, combined drug action from the combination of Oxa with the phytochemicals andrographolide (Andro), epigallocatechin-3-gallate (EGCG), chlorophyllin (Chl), colchicines (Col), curcumin (Cur) and paclitaxel (Tax) was evaluated in the human ovarian cancer cell lines A2780 and A2780(cisR). The combination index (CI) was used as a measure of synergism (CI<1), addictiveness (CI=1) and antagonism (CI>1). Generally, all the combinations showed greater synergism at a lower concentration (ED(50)) than at higher concentrations (ED(75) and ED(90)). Oxa in binary combination with Col and Tax showed the highest synergism in both the cancer cell lines, when administered 4 h after the phytochemical, with CI at ED(50) ranging from 0.004 to 0.1. The combination of Oxa with the other phytochemicals generally showed greater synergism when Oxa was administered 4 h before the phytochemical. Appropriately sequenced combination of Oxa with tumor active phytochemicals produces marked synergistic effects in cisplatin resistant as well as non-resistant ovarian cancer cell lines and may offer the means of overcoming drug resistance in ovarian cancer.
authors.affiliation: Discipline of Biomedical Science, Sydney Medical School, Cumberland Campus C42, The University of Sydney, Lidcombe 2141, NSW, Australia.
authors.forename: Nurhanan M
authors.initials: NM
authors.lastname: Yunos
authors.forename: Philip
authors.initials: P
authors.lastname: Beale
authors.forename: Jun Qing
authors.initials: JQ
authors.lastname: Yu
authors.forename: Fazlul
authors.initials: F
authors.lastname: Huq
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D000077150:Oxaliplatin
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin