Clin Epigenetics. 2011 Aug;2(2):339-48. doi: 10.1007/s13148-010-0019-x. Epub 2011 Jan 15.
While studying on epigenetic regulatory mechanisms (DNA methylation at C-5 of -CpG- cytosine and demethylation of methylated DNA) of certain genes (FAS, CLU, E-cadh, CD44, and Cav-1) associated with prostate cancer development and its better management, we noticed that the used in vivo dose of 5-aza-2'-deoxycytidine (5.0 to 10.0 nM, sufficient to inhibit DNA methyltransferase activity in vitro) helped in the transcription of various genes with known (steroid receptors, AR and ER; ER variants, CD44, CDH1, BRCA1, TGFβR1, MMP3, MMP9, and UPA) and unknown (DAZ and Y-chromosome specific) proteins and the respective cells remained healthy in culture. At a moderate dose (20 to 200 nM) of the inhibitor, cells remain growth arrested. Upon subsequent challenge with increased dose (0.5 to 5.0 μM) of the inhibitor, we observed that the cellular morphology was changing and led to death of the cells with progress of time. Analyses of DNA and anti-, pro-, and apoptotic factors of the affected cells revealed that the molecular events that went on are characteristics of programmed cell death (apoptosis).
在研究与前列腺癌发展及其更好管理相关的某些基因（FAS、CLU、E-cadh、CD44 和 Cav-1）的表观遗传调控机制（C-5 的 -CpG-胞嘧啶的 DNA 甲基化和甲基化 DNA 的去甲基化）时，我们注意到，体内使用的 5-氮杂-2'-脱氧胞苷（5.0 至 10.0 nM，足以抑制体外 DNA 甲基转移酶活性）有助于转录各种具有已知（甾体受体、AR 和 ER；ER 变体、CD44、CDH1、BRCA1、TGFβR1、MMP3、MMP9 和 UPA）和未知（DAZ 和 Y 染色体特异性）蛋白的基因，并且相应的细胞在培养中保持健康。在抑制剂的中等剂量（20 至 200 nM）下，细胞仍处于生长停滞状态。随后用增加剂量（0.5 至 5.0 μM）的抑制剂进行后续挑战时，我们观察到细胞形态发生变化，并随着时间的推移导致细胞死亡。受影响细胞的 DNA 分析以及抗、促和凋亡因子的分析表明，发生的分子事件是程序性细胞死亡（凋亡）的特征。
