Radiosensitivity of human prostate cancer cells can be modulated by inhibition of 12-lipoxygenase |
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| Authors: | J. Lö vey,D. Nie,J. Tó vá ri,I. Kenessey,J. Tí má r,M. Kandouz,K.V. Honn |
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| Affiliation: | 1. Departments of Radiotherapy and Experimental Therapeutics, National Institute of Oncology, Budapest, Hungary;2. Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, United States;3. Department of Experimental Pharmacology, National Institute of Oncology, Budapest, Hungary;4. 2nd Department of Pathology, Semmelweis University, Budapest, Hungary;5. Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48202, United States;6. Karmanos Cancer Institute, Detroit, MI 48202, United States;g Bioactive Lipids Research Program, Detroit, MI 48202, United States |
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| Abstract: | Nearly 30% of prostate cancer (PCa) patients treated with potentially curative doses relapse at the sites of irradiation. How some tumor cells acquire radioresistance is poorly understood. The platelet-type 12-lipoxygenases (12-LOX)-mediated arachidonic acid metabolism is important in PCa progression. Here we show that 12-LOX confers radioresistance upon PCa cells. Treatment with 12-LOX inhibitors baicalein or BMD122 sensitizes PCa cells to radiation, without radiosensitizing normal cells. 12-LOX inhibitors and radiation, when combined, have super additive or synergistic inhibitory effects on the colony formation of both androgen-dependent LNCaP and androgen-independent PC-3 PCa cells. In vivo, the combination therapy significantly reduced tumor growth. |
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| Keywords: | 12-Lipoxygenase 12(S)-HETE Prostate cancer Radiation therapy Radioresistance |
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