[Selective 12-lipoxygenase inhibition potentiates the effect of radiation on human prostate cancer cells in vitro and in vivo].

Abstract

Prostate cancer is one of the leading cancer types in males in the developed world. Radiotherapy is a major method in the curative treatment of prostate cancer however, up to 30% of the patients experience local relapse. Arachidonic acid metabolites have been shown to have important role in cancer. 12-lipoxygenase (12-LOX) has been proven to significantly influence prostate cancer progression, by apoptosis regulation and by promoting cancer cell survival. In this study we examined whether 12-LOX inhibition may increase radiation sensitivity of prostate cancer cells in vitro and in vivo. Prostate cancer cell lines were treated with 12-LOX inhibitors, different doses of radiation and the combination of 12-LOX inhibitors and radiation. We measured the effect of these treatments through clonogenic survival and apoptosis in vitro and tumor growth in vivo in a tumor xenograft model. 12-LOX inhibition and radiation both increased apoptosis and decreased clonogenic survival of prostate cancer cell lines in vitro. Combined treatment resulted in a supra-additive effect in vitro. In vivo both 12-LOX inhibition and radiotherapy caused delay in growth of the xenograft tumors but the combined treatment resulted in the strongest growth inhibition. The presented data prove that 12-LOX and its metabolite 12(S)-HETE have a major role in prostate cancer cell progression and radiosensitivity. We have shown by different methods in vitro and in vivo that inhibition of 12-LOX activity significantly sensitizes prostate cancer cells to radiation. Therefore we can state that 12-LOX inhibitors are promising compounds to be developed to become a new class of clinical radiation sensitizers in prostate cancer.

• Authors: József Lövey, Daotai Nie, József Tóvári, István Kenessey, Mahmout Kandouz, József Tímár, Miklós Kásler, Kenneth V Honn
• Journal: Magyar onkologia (Magy Onkol) Vol. 58 Issue 3 Pg. 211-8 (Sep 2014) ISSN: 0025-0244 [Print] Hungary
• Vernacular Title: Humán prosztatarák sugárérzékenységének fokozása szelektív 12-lipoxigenáz-gátlással preklinikai modellben.
• PMID: 25260086 (Publication Type: English Abstract, Journal Article)

Chemical References

• 12-hydroxyeicosatetraenoic acid receptor
• Lipoxygenase Inhibitors
• Receptors, Eicosanoid
• Arachidonate 12-Lipoxygenase

Topics

• Apoptosis (radiation effects)
• Arachidonate 12-Lipoxygenase (metabolism)
• Cell Line, Tumor (radiation effects)
• Cell Survival (radiation effects)
• Disease Progression
• Humans
• Lipoxygenase Inhibitors (pharmacology)
• Male
• Prostatic Neoplasms (pathology, radiotherapy)
• Radiation Tolerance (drug effects)
• Receptors, Eicosanoid (drug effects, metabolism)
• Xenograft Model Antitumor Assays