Monoamine oxidase inhibitors l-deprenyl and clorgyline protect nonmalignant human cells from ionising radiation and chemotherapy toxicity.
Cell Culture Techniques
Cell Transformation, Neoplastic
Monoamine Oxidase Inhibitors
Tumor Cells, Cultured
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CitationMonoamine oxidase inhibitors l-deprenyl and clorgyline protect nonmalignant human cells from ionising radiation and chemotherapy toxicity. 2003, 89 (10):1979-86 Br. J. Cancer
JournalBritish journal of cancer
Abstractl-Deprenyl (R-(-)-deprenyl, selegiline) is an inhibitor of monoamine oxidase-B (MAO-B) that is known to protect nerve cells from a variety of chemical and physical insults. As apoptosis is a common mechanism of radiation-induced cell death, the effect of l-deprenyl on the survival of cultured cells and tissue explants was studied following exposure to gamma radiation. The results obtained were compared with the effects of the less-selective MAO-B inhibitor pargyline and the MAO-A inhibitor clorgyline. l-Deprenyl at a concentration of 10(-9) M protected the nontumorigenic cell line (HaCaT) and normal human urothelial explants from the effects of cobalt-60 gamma radiation, but did not protect tumorigenic human cell lines HaCaT-ras, HPV-transfected human keratinocytes (HPV-G cells), or PC3. Human bladder carcinoma explants were not protected. Clorgyline showed a smaller protective effect of normal cells, whereas pargyline had no effect. Radiation-induced delayed effects (genomic instability measured as delayed cell death) were prevented in normal cells by l-deprenyl but, interestingly, deprenyl appeared to increase the amount of delayed death in the tumorigenic cell lines. Studies using l-deprenyl prior to the exposure of nonmalignant cells to cisplatin showed that cell death due to this agent was also reduced. Treatment of cultures of nontumorigenic cells with l-deprenyl or clorgyline significantly increased the levels of the protein Bcl-2 following irradiation, but there was no such effect on the already-elevated levels of this protein in the tumour samples. Since the Bcl-2 has been shown to be an inhibitor of apoptosis or programmed cell death, this would imply that the protective effects of l-deprenyl and clorgyline involve activation of antiapoptotic pathways within the normal cell. This hypothesis is supported by data showing reduced levels of apoptosis in HaCAT cells and in normal bladder explant cultures following treatment with l-deprenyl.
- Thyroid iodide transport is reduced by administration of monoamine oxidase A inhibitors to rats.
- Authors: Cabanillas AM, Masini-Repiso AM, Costamagna ME, Pellizas C, Coleoni AH
- Issue date: 1994 Nov
- Potentiation of para-hydroxyamphetamine-induced head-twitch response by inhibition of monoamine oxidase type A in the brain.
- Authors: Tadano T, Satoh S, Satoh N, Kisara K, Arai Y, Kim SK, Kinemuchi H
- Issue date: 1989 Jul
- Effect of nonselective and selective inhibitors of monoamine oxidases A and B on pethidine toxicity in mice.
- Authors: Boden R, Botting R, Coulson P, Spanswick G
- Issue date: 1984 May
- Inhibition of MAO-A activity enhances behavioural activity of rats assessed using water maze and open arena tasks.
- Authors: Barbelivien A, Nyman L, Haapalinna A, Sirviö J
- Issue date: 2001 Jun
- Modulation of glutamate neurotoxicity in the transformed cell culture by monoamine oxidase inhibitors, clorgyline and deprenyl.
- Authors: Abakumova OYu, Podobed OV, Tsvetkova TA, Yakusheva IV, Moskvitina TA, Kondakova LI, Navasardyantz DG, Medvedev AE
- Issue date: 1998