Antiproliferative activity of polymer-bound, monoamine-coordinated platinum complexes against LNCaP human metastatic prostate adenocarcinoma cells

The chemotherapeutic treatment of secondary, i.e., disseminated cancers, has until now remained an unsatisfactory modality. The LNCaP human metastatic prostate adenocarcinoma cell line lends itself as a useful tool to probe the efficaciousness of novel antineoplastic agents for the control of metastatic cell growth. In this paper we report on a series of cell culture tests assessing the antiproliferative activity of several water-soluble polymer-platinum conjugates in which the metal is tied (anchored) to various polymeric carriers through coordination by a single carrier-attached primary amine ligand. The conjugates are based on polyaspartamide carriers composed, within the backbone, of a majority fraction of subunits bearing water-solubilizing tertiary amine side-group functions and a minority fraction of subunits featuring side chain-terminating primary amino groups for metal binding. Two similarly structured conjugates in which the platinum center is coordinated by two amine ligands in cisoid orientation mimicking the structural skeleton of cisplatin are included in the study for comparison. In all structures cleavage of a side-chain segment is required for release of the monomeric bioactive platinum complex. The growth of LNCaP human metastatic prostate adenocarcinoma cells in RPMI 1640 medium in the presence and absence of the conjugates in a range of concentrations is assessed by a protein assay, and the IC50 values, representing the drug concentrations required for 50% cell growth inhibition relative to untreated control, are determined. The results show both classes of conjugates, those comprising monoamine-coordinated platinum and those featuring cis-diamine-coordinated metal, to be well comparable in antiproliferative activity. A major program of synthesis and evaluation of polymer-bound monoamineplatinum complexes, prompted by these findings, is forthcoming in this laboratory. © 2000 Plenum Publishing Corporation.