Studies from University of Michigan, Comprehensive Cancer Center have provided new data on prostate cancer therapy
December 22nd, 2008
2008 DEC 22 -- Current study results from the report, 'Molecularly targeted radiosensitization of human prostate cancer by modulating inhibitor of apoptosis,' have been published. "The inhibitor of apoptosis proteins (IAP) are overexpressed in hormone-refractory prostate cancer, rendering the cancer cells resistant to radiation. This study aims to investigate the radiosensitizing effect of small-molecule IAP inhibitor both in vitro and in vivo in androgen-independent prostate cancer and the possible mechanism of radiosensitization," scientists writing in the journal Clinical Cancer Research report.
"Radiosensitization of SH-130 in human prostate cancer DU-145 cells was determined by clonogenic survival assay. Combination effect of SH-130 and ionizing radiation was evaluated by apoptosis assays. Pull-down and immunoprecipitation assays were employed to investigate the interaction between SH-130 and IAPs. DU-145 xenografts in nude mice were treated with SH-130, radiation, or combination, and tumor suppression effect was determined by caliper measurement or bioluminescence imaging. Nuclear factor-kappaB activation was detected by luciferase reporter assay and quantitative real-time PCR. SH-130 potently enhanced radiation-induced caspase activation and apoptosis in DU-145 cells. Both X-linked IAP and cIAP-1 can be pulled down by SH-130 but not by inactive SH-123. Moreover, SH-130 interrupted interaction between X-linked IAP/cIAP-1 and Smac. In a nude mouse xenograft model, SH-130 potently sensitized the DU-145 tumors to X-ray radiation without increasing systemic toxicity. The combination therapy suppressed tumor growth more significantly than either treatment alone, with over 80% of complete tumor regression. Furthermore, SH-130 partially blocked tumor necrosis factor-alpha-and radiation-induced nuclear factor-kappaB activation in DU-145 cells. Our results show that small-molecule inhibitors of IAPs can overcome apoptosis resistance and radiosensitize human prostate cancer with high levels of IAPs," wrote Y. Dai and colleagues, University of Michigan, Comprehensive Cancer Center.
The researchers concluded: "Molecular modulation of IAPs may improve the outcome of prostate cancer radiotherapy."
Dai and colleagues published their study in Clinical Cancer Research (Molecularly targeted radiosensitization of human prostate cancer by modulating inhibitor of apoptosis. Clinical Cancer Research, 2008;14(23):7701-10).
Additional information can be obtained by contacting Y. Dai, University of Michigan Comprehensive Cancer Center, Dept. of Radiation Oncology, Ann Arbor, Michigan 48109-0582 USA..
The publisher of the journal Clinical Cancer Research can be contacted at: American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.
Keywords: United States, Ann Arbor, Prostate Cancer Therapy, Apoptosis, Bioluminescence, Biotechnology, Cancer Research, Enzymology, Experimental Design, Hormones, Luciferase, Oncology, Prostate Cancer, Prostatic Neoplasms, Therapy, Treatment, Tumor Suppression, Xenograft, Xenotransplantion.
This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2008, Biotech Business Week via NewsRx.com.
