The combination of gamma ionizing radiation and 8-Cl-cAMP induces synergistic cell growth inhibition and induction of apoptosis in human prostate cancer cells.
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| Abstract |
The antiproliferative and cytotoxic potential of the nucleotide analog 8-Cl-cAMP was tested in PC-3 and DU145 metastatic human prostate cancer cells. The drug was examined as the only therapeutic agent and in combination with ionizing irradiation (IR). Highly synergistic effects of IR and 8-Cl-cAMP were observed in both cell lines when examined by the MTT viability and BrdU proliferation assays. The combination of IR and 8-Cl-cAMP at clinically relevant doses exerted substantial growth inhibition. The combination of IR and 8-Cl-cAMP caused a significant disturbance in the distribution of cell cycle phases. Cell cycle arrest in the sub-G0/G1 phase predominated in both cell lines. The most striking observation was a significant increase in apoptotic PC-3 and DU145 cells. The DU145 cells were three times more sensitive to the combined treatment than PC-3 cells. The initial resistance to IR-induced apoptosis in these p53-deficient prostate cancer cell lines was overcome through an alternative proapoptotic pathway induced by 8-Cl-cAMP. Considering the low effective doses of treatments, improved tumor eradication rates and minimal undesirable side effects, the combination of IR and 8-Cl-cAMP could be the therapy of choice in treating prostate cancer.
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| Authors | Vesna Vucić, Ana Nićiforović, Miroslav Adzić, Marija B Radojcić, Sabera Ruzdijić |
| Journal | Investigational new drugs (Invest New Drugs) Vol. 26 Issue 4 Pg. 309-17 (Aug 2008) ISSN: 0167-6997 [Print] United States |
| PMID | 18060599 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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