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: J Lövey, D Nie, J Tóvári, I Kenessey, J Tímár, M Kandouz, K V Honn
• Journal: Cancer letters (Cancer Lett) Vol. 335 Issue 2 Pg. 495-501 (Jul 28 2013) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 23523613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Flavanones
• Lipoxygenase Inhibitors
• Arachidonic Acid
• baicalein
• Arachidonate 12-Lipoxygenase

Topics

• Animals
• Apoptosis (radiation effects)
• Arachidonate 12-Lipoxygenase (metabolism)
• Arachidonic Acid (metabolism)
• Cell Line, Tumor
• Flavanones (pharmacology)
• Gene Expression Regulation, Neoplastic
• Humans
• Lipoxygenase Inhibitors (pharmacology)
• Male
• Mice
• Mice, SCID
• Prostatic Neoplasms (radiotherapy)
• Radiation Tolerance