Synthesis of tris(quinoline)monochloroplatinum(II) Chloride and its Activity Alone and in Combination with Capsaicin and Curcumin in Human Ovarian Cancer Cell Lines.
Currently used platinum drugs fail to provide long-term cure for ovarian cancer mainly because of acquired drug resistance. With the idea that the difference may translate into an altered spectrum of activity, monofunctional planaramineplatinum(II) complex tris(quinoline)monochloro-platinum chloride (coded as LH5) was synthesized and investigated for its activity against human ovarian A2780, cisplatin-resistant A2780 (A2780(cisR)) and ZD0473-resistnat A2780 (A2780(ZD0473R)) cancer cell lines alone and in combination with the phytochemicals capsaicin (Caps) and curcumin (Cur) as a function of concentration and sequence of administration. Cell viability was quantified using the MTT reduction assay, while combination was used as a quantitative measure of the combined drug action. LH5 is found to be more active than cisplatin (CS) against both resistant cell lines. Combination of LH5 with capsaicin showed synergism in all three cell lines, with the bolus being most synergistic. Lack of association between the levels of platinum accumulation and platinum-DNA with cytotoxicity can be seen to indicate that binding with DNA may not be the main determinant of activity of LH5. Greater activity of LH5 compared to cisplatin, especially against the resistant cell lines, indicates that the compound may have the potential for development as a novel anticancer drug and that its combination with phytochemicals can serve to further enhance drug efficacy.
Discipline of Biomedical Science, Sydney Medical School, The University of Sydney, Lidcombe, NSW, Australia.
Laila
L
Arzuman
Sydney Cancer Centre, Concord Hospital, Concord, NSW, Australia.
Philip
P
Beale
Discipline of Biomedical Science, Sydney Medical School, The University of Sydney, Lidcombe, NSW, Australia.
Jun Q
JQ
Yu
Discipline of Biomedical Science, Sydney Medical School, The University of Sydney, Lidcombe, NSW, Australia Fazlul.Huq@sydney.edu.au.
Fazlul
F
Huq
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D006801:Humans; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010984:Platinum / Q000378:metabolism
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C000613698:monofunctional planaramineplatinum(II) complex tris(quinoline)monochloro-platinum chloride; D010984:Platinum; D004247:DNA; D003474:Curcumin; D002211:Capsaicin
Quinoline; drug combination; drug resistance; monofunctional platinum; ovarian cancer