Radiosensitivity of human prostate cancer cells can be modulated by inhibition of 12-lipoxygenase

Cancer Lett. 2013 Jul 28;335(2):495-501. doi: 10.1016/j.canlet.2013.03.012. Epub 2013 Mar 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


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