title: Radiosensitivity of human prostate cancer cells can be modulated by inhibition of 12-lipoxygenase.
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.
authors.affiliation: Departments of Radiotherapy and Experimental Therapeutics, National Institute of Oncology, Budapest, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Lövey
authors.forename: D
authors.initials: D
authors.lastname: Nie
authors.forename: J
authors.initials: J
authors.lastname: Tóvári
authors.forename: I
authors.initials: I
authors.lastname: Kenessey
authors.forename: J
authors.initials: J
authors.lastname: Tímár
authors.forename: M
authors.initials: M
authors.lastname: Kandouz
authors.forename: K V
authors.initials: KV
authors.lastname: Honn
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism*; D045744:Cell Line, Tumor; D044950:Flavanones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011836:Radiation Tolerance
chemical_list: D044950:Flavanones; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; C006680:baicalein; D001092:Arachidonate 12-Lipoxygenase