Suramin is a novel cytostatic/cytotoxic agent that is currently undergoing clinical trials in the treatment of hormone- and chemo-refractory tumors. Its unusual mechanism of action and its activity against prostate cancer raise the possibility that it could be particularly suitable for combined-modality treatment of prostate cancer. PC3 human prostate cancer cells were used as an in vitro model to test the possible interaction between suramin and ionizing radiation. Treatment with γ radiation resulted in detachment of PC3 cells from the monolayer, and the detached cells exhibited internucleosomal DNA fragmentation characteristic of apoptosis. Low concentrations of suramin (50-100 μg/ml, 35-70 μM) increased spontaneous as well as radiation-enhanced apoptosis. However, suramin inhibited spontaneous and radiation-enhanced apoptosis at 300 μg/ml (210 μM), a concentration that is more commonly used in the clinic. At this concentration suramin inhibited DNA fragmentation induced by chemotherapeutic drugs as well. The effect of suramin on inhibition of DNA fragmentation was reversible if the suramin was removed 24 h after irradiation. Despite inhibition of radiation- induced apoptosis by 300 μg/ml suramin (from 5% to 2.9% at 48 h), clonogenic cell death was enhanced by the combination of suramin and radiation. The effects of radiation and suramin on clonogenic cell survival appeared to be additive by isobologram analysis at clinically relevant radiation doses. Continuous exposure to a lower concentration of suramin (100 μg/ml) during the clonogenic assay period was as effective in decreasing clonogenic survival as 48 h exposure to 300 μg/ml suramin in decreasing clonogenic survival. Our data indicate that, when used in combination with radiation, suramin may be effective at concentrations that are lower than those required for efficacy as a single agent.
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging