5-Azacytidine modulates gamma-glutamyltransferase and glutathione levels in two human prostatic adenocarcinoma cell lines.
Two human prostate adenocarcinoma cell lines, LNCaP and PC-3, were used to study the effect of 5-azacytidine on GGT gene expression, via genomic DNA methylation, and GSH content. When the cells were treated with 5-azaC, the specific GGT activity increased in a dose and time-dependent manner and was accompanied by the elevation of intracellular glutathione content. Southern blot analysis of DNA digested with MspI or HpaII showed negative correlation between the methylation pattern of GGT DNA and GGT activity, either in control or 5-azaC treated cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that GGT mRNA types I are expressed and induced in a cell type-specific manner in control and 5-azacC treated cells respectively. Overall, our investigations suggest that DNA methylation and other mechanisms combine to regulate GGT gene expression in studied prostate adenocarcinoma derived cells.
el Yaagoubi
M
M
Centre du Médicament, UPRES, Faculty of Pharmacy, UHP Nancy I, France.
Visvikis
A
A
Khalid
A
A
Siest
G
G
Wellman
M
M
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D001374:Azacitidine / Q000494:pharmacology*; D015139:Blotting, Southern; D019175:DNA Methylation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008297:Male; D010920:Placenta / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D005723:gamma-Glutamyltransferase / Q000235:genetics* / Q000378:metabolism
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D001374:Azacitidine