Role of glyoxalase I in the proliferation and apoptosis control of human LNCaP and PC3 prostate cancer cells.
BACKGROUND
Glyoxalase I (GLOI) detoxifies reactive dicarbonyls, as methylglyoxal (MG) that, directly or through the formation of MG-derived adducts, is a growth inhibitor and apoptosis inducer. GLOI has been considered a general marker of cell proliferation, but a direct link between the two has yet to be demonstrated. The aim of the present work was to clarify whether GLOI was involved in the proliferation control of LNCaP and PC3 human prostate cancer cells or might play a different role in the growth regulation of these cells.


METHODS
RNA interference was used to study the role of GLOI in cell proliferation or apoptosis. Cell proliferation was evaluated by [3H]thymidine incorporation assay and flow cytometry, that was also used to analyze apoptosis. Real-time TaqMan polymerase chain reaction and spectrophotometric analyses were used to study transcript levels or specific activity, respectively. Proteins levels were analyzed by Western blot. MG was measured by high-performance liquid chromatography.


RESULTS
We found that GLOI is not implicated in the proliferation control of LNCaP and PC3 cells but plays a role in the apoptosis of invasive prostate cancer PC3 cells, through a mechanism involving a specific MG-adduct and NF-kB signaling pathway.


CONCLUSIONS
Our data represent the first systematic demonstration that GLOI cannot be considered a general marker of cell proliferation and that acts as a pro-survival factor in invasive PC3 cells by elusing apoptosis. GLOI may be involved in prostate cancer progression, via the control of key molecules in the mitochondrial apoptotic mechanism, through NF-kB signaling pathway.
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Cinzia
C
Antognelli
Letizia
L
Mezzasoma
Katia
K
Fettucciari
Ettore
E
Mearini
Vincenzo N
VN
Talesa
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000502:physiology*; D008297:Male; D024101:Mitochondrial Proteins / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D024101:Mitochondrial Proteins; D016328:NF-kappa B; D007791:Lactoylglutathione Lyase