Session Speaker

Toward New Platinums in Ovarian Cancer
Fazlul Huq, Philip Beale, Jun Qing Yu, Ali Alshehri, Nurhanan M Yunos and Shahnaz Alqassab
Australia

Although cisplatin, and its analogues carboplatin and oxaliplatin are widely used to kill cancerous cells, they have a limited spectrum of activity. With the idea that a more significant change in the spectrum of activity of platinum drugs can be achieved by altering the mode of binding with DNA, considerable research effort has been directed at rule-breaker platinum compounds. We have also synthesized a number of mononuclear trans-planaramine platinum(II) complexes of the forms: trans-[Pt(NH3)LCl2] and trans-[PtLL'Cl2 where L and L' stand for a planaramine ligand and multicentred platinum compounds some containing one or two planaramine ligands bound to the central metal ion. One complex of the form: trans-[Pt(NH3)LCl2] where L is (1,2-a)pyridine (code named YH12) is found to be significantly more active than cisplatin against ovarian A2780cisR cancer cell line. It has a resistance factor of 0.5 indicating increased activity in the resistant cell line. A number of tri-nuclear complexes in which the central metal ion is bound to one or two planaramine ligands have also been synthesized. Six of the compounds code named DH6Cl, CH9, CH25, TH1 QH1 and QH5 have been found to be significantly more active than cisplatin in a number of ovarian cancer cell lines. In an attempt to overcome drug resistance and reduce side effects, we have treated human ovarian cancer cells with combinations of platinums and selected phytochemicals. The results of the study show that cisplatin and designed platinums show both sequence- and dose-dependent synergism in activity when combined with plant compounds. We have also carried out proteomic studies to determine changes in expression of key proteins associated with resistance. This presentation will review the work done in our laboratory on platinum-based tumour active compounds.