title: Studies on combination of platinum drugs cisplatin and oxaliplatin with phytochemicals anethole and curcumin in ovarian tumour models.
abstract: Chemopreventative phytochemicals having antitumour and antioxidant properties can overcome problems of chemoresistance and nonspecific toxicity towards normal cells that are associated with platinum-based chemotherapy against cancer. These agents exert their effects by bringing into play numerous cellular proteins that in turn affect multiple steps in pathways leading to tumourigenesis. In this study, combinations of two cytotoxic phytochemicals anethole and curcumin were applied in binary combination with platinum drugs cisplatin and oxaliplatin to three epithelial ovarian cancer cell lines: A2780 (parent), A2780(cisR) (cisplatin-resistant) and A2780(ZD0473R) (ZD0473-resistant). Cell viability was quantified using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay and the combined drug action was analyzed based on the equations derived by Chou and Talalay (1984). Greatest synergism was observed when the phytochemical was added first followed by the platinum drug 2 h later and additiveness to antagonism in combined drug action was observed when the two compounds were administered as a bolus. If confirmed in vivo, the appropriate sequenced combinations of platinum with the phytochemicals may provide a means of overcoming drug resistance.
authors.affiliation: Discipline of Biomedical Science, School of Medical Sciences, Sydney Medical School, The University of Sydney, Cumberland Campus C42, 75 East Street, Lidcombe, NSW 1825, Australia.
authors.forename: Meher U
authors.initials: MU
authors.lastname: Nessa
authors.forename: Philip
authors.initials: P
authors.lastname: Beale
authors.forename: Charles
authors.initials: C
authors.lastname: Chan
authors.forename: Jun Q
authors.initials: JQ
authors.lastname: Yu
authors.forename: Fazlul
authors.initials: F
authors.lastname: Huq
mesh_terms: D000081248:Allylbenzene Derivatives; D000840:Anisoles / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage; D003474:Curcumin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms; D000077150:Oxaliplatin; D008517:Phytotherapy / Q000379:methods*
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003474:Curcumin; D002945:Cisplatin; C006578:anethole