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Finding Novel Platinum(II)-Based Anti-Cancer Drugs with Reduced Hearing Side-Effects
Jerry D. Monroe1, Kevin M. Williams2, Michael E. Smith1
1
Department of Biology, Western Kentucky University, Bowling Green, KY
2
Department of Chemistry, Western Kentucky University, Bowling Green, KY
Background and Objective:
Recently synthesized heterocyclic- and triamine-liganded platinum(II) compounds bind DNA
differently than traditional diamine-liganded platinum chemotherapy drugs and could produce
reduced side-effects by signaling through different cellular pathways. This project investigates
whether several new platinum(II) compounds target cancer cells without producing hearing sideeffects.
Methods:
Four novel platinum(II) compounds, phenanthriplatin, pyriplatin, Pt(dien)Cl, and Pt(Et2dien)Cl,
were tested in five cancer cell lines [HTB-16 (glioma), Saos-2 (osteosarcoma), A549 (lung),
MCF-7 (breast), Caco-2 (colorectal)] and a non-cancer control line [IMR-90 (fibroblast)]. The 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a fluorescent
cytotoxicity assay were used to quantify cellular viability and cytotoxicity. Zebrafish were
injected with platinum compounds or a 0.9% NaCl vehicle control and were given hearing tests
using the auditory evoked potential technique. Their inner ears were then dissected out and
their hair cells and apoptotic cells were quantified using phalloidin and terminal deoxynucleotidyl
transferase dUTP nick end labeling (TUNEL) staining.
Results:
Our preliminary results suggest that these novel platinum compounds target cancer cells but
that all the compounds but pyriplatin produce some hearing side-effects and these chemicals
can damage auditory tissue.
Discussion and Conclusions:
Novel heterocyclic- and triamine-liganded platinum(II) compounds can act against cancer as
effectively as diamine-liganded compounds such as cisplatin. Some of these new compounds
may cause hearing loss and auditory tissue damage.
Supported by INBRE grant NIGMS 8P20GM103436 and NIH grant 1 R15 CA188890-01A1.