title: Synergism from combinations of tris(benzimidazole) monochloroplatinum(II) chloride with capsaicin, quercetin, curcumin and cisplatin in human ovarian cancer cell lines.
abstract: In the present study, synergism in activity from the sequenced combinations of monofunctional platinum tris(benzimidazole)monochloroplatinum(II) chloride (coded as LH4) with capsaicin, quercetin, curcumin and cisplatin was investigated as a function of sequence of administration in a number of human ovarian tumor models. Cellular accumulations of platinum and the levels of platinum-DNA binding were also determined for the 0/0 h and 4/0 sequences of administration. LH4 was found to be more active against the resistant A2780(cisR) and A2780(ZD0473R) cell lines than the parent A2780 cell line. As applied to combinations of LH4 with phytochemicals capsaicin, quercetin and curcumin, bolus administration was found to be most synergistic in both the parent A2780 and the resistant A2780(cisR) cell lines. For the combinations of LH4 with cisplatin, additiveness was observed in both the resistant cell lines but mild synergism was observed in the parent cell line. Greater activity of designed monofunctional platinum LH4 against resistant tumor models and synergism from combinations with phytochemicals indicate that the compound has the potential for development as a novel platinum-based anticancer drug.
authors.affiliation: Discipline of Biomedical Science, Sydney Medical School, The University of Sydney, Lidcombe, NSW, Australia.
authors.forename: Laila
authors.initials: L
authors.lastname: Arzuman
authors.affiliation: Sydney Cancer Centre, Concord Hospital, Concord, NSW, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Beale
authors.affiliation: Department of Pathology, Concord Hospital, Concord, NSW, Australia.
authors.forename: Charles
authors.initials: C
authors.lastname: Chan
authors.affiliation: Discipline of Biomedical Science, Sydney Medical School, The University of Sydney, Lidcombe, NSW, Australia.
authors.forename: Jun Q
authors.initials: JQ
authors.lastname: Yu
authors.affiliation: Discipline of Biomedical Science, Sydney Medical School, The University of Sydney, Lidcombe, NSW, Australia Fazlul.Huq@sydney.edu.au.
authors.forename: Fazlul
authors.initials: F
authors.lastname: Huq
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D018736:DNA Adducts; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D020128:Inhibitory Concentration 50; D008954:Models, Biological; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D018736:DNA Adducts; D009944:Organoplatinum Compounds; D011794:Quercetin; C031000:benzimidazole; D003474:Curcumin; D002945:Cisplatin; D002211:Capsaicin
keywords: Benzimidazole; drug combination; drug resistance; monofunctional platinum; ovarian cancer