title: Synergism from combinations of cisplatin and oxaliplatin with quercetin and thymoquinone in human ovarian tumour models.
abstract: The development of drug resistance remains one of the major hurdles in cancer chemotherapy, particularly so for ovarian cancer. Combination of drugs acting synergistically in combination can offer a means of overcoming drug resistance. In this study, two tumour-active phytochemicals, quercetin and thymoquinone, were combined with two platinum drugs, cisplatin and oxaliplatin, with the aim of providing a means of overcoming drug resistance. Two human epithelial ovarian cancer cell lines, A2780 and its cisplatin-resistant form (A2780(cisR)) were treated with binary combinations of cisplatin and oxaliplatin with quercetin and thymoquinone using three sequences of administration. Cell viability was quantified using the (MTT) reduction assay. The combined drug action was analysed based on the equations derived by Chou and Talalay (1984). Greatest synergism was observed when the phytochemical was added first followed by platinum drug 2 h later and the least synergism (often additive to antagonistic) was observed when the two compounds were administered as a bolus. It is suggested that the addition of the phytochemical 2 h before platinum drug may sensitize cancer cells to platinum action, thus offering a means of overcoming drug resistance. The results may be highly significant clinically if found to be confirmed in vivo.
authors: 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: Meher U
authors: MU
authors: Nessa
authors: Philip
authors: P
authors: Beale
authors: Charles
authors: C
authors: Chan
authors: Jun Q
authors: JQ
authors: Yu
authors: Fazlul
authors: F
authors: Huq
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology*; D002470:Cell Survival; D002945:Cisplatin / Q000008:administration & dosage; D004357:Drug Synergism; D005260:Female; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077150:Oxaliplatin; D011794:Quercetin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000975:Antioxidants; D016227:Benzoquinones; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D011794:Quercetin; C003466:thymoquinone; D002945:Cisplatin